A few years ago no one would have suspected that the well‐known disorder of connective tissue, Marfan syndrome, could be caused by mutations in a recently discovered extracellular component, fibrillin. Likewise, nobody would have predicted that fibrillin represents a small family of proteins that are associated with several pheno‐typically overlapping disorders. The fibrillins are integral constituents of the non‐collagenous microfibrils, with an average diameter of 10 nm. These aggregates are distributed in the extracellular matrix of virtually every (...) class='Hi'>tissue. Microfibrillar bundles provide the external coating to elastin in elastic fibers, and serve an anchoring function in non‐elastic tissues. At higher resolution, individual microfibrils have a “beads‐on‐a‐string” appearance resulting from the head‐to‐tail polymerization of multiple fibrillin aggregates. Structurally, fibrillin contains a series of repeated sequences homologous to the epidermal growth factor calcium‐binding motif. Characterization of fibrillin mutations in Marfan syndrome patients, together with the elucidation of the structure of the fibrillin proteins, have provided new insights, and raised new questions, about the function of the 10 nm microfibrils. For example, it is possible that the fibrillins, in addition to serving a structural function, might also be involved in regulating cellular activities and morphogenetic programs. It is fitting that the long search for the Marfan syndrome gene has brought a novel group of proteins to the forefront of extracellular matrix biology. (shrink)

Collagen fibrils are some of the most‐abundant and important extracellular structures in our bodies, yet we are unsure of their shape and size. This is largely due to an inherent difficulty in isolating them from their surrounding tissues. Echinoderms have collagenous tissues that are similar to ours in many ways, yet they can be manipulated to easily relinquish their collagen fibrils, providing an excellent opportunity to study native fibrillar structure. In the early 1990s, they were found to defy the (...) commonly accepted fibrillar model of the time in that they were much shorter, they were shaped like double‐ended spindles, and their centers exhibited a reversal in molecular polarity. Realization of these features helped to reform the questions that were being asked about vertebrate fibrils, shifting the focus toward shape and size. Since then, researchers working with both groups (echinoderms and vertebrates) have worked together to find the structure of native fibrils. This information will be fundamental in understanding what holds collagenous tissues together at the fibrillar level, and could have important implications for people with Ehlers‐Danlos syndrome. BioEssays 29:645–653, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

ObjectiveTo explore alterations in white matter network topology in de novo Parkinson's disease patients with rapid eye movement sleep behavior disorder.Materials and MethodsThis study included 171 de novo PD patients and 73 healthy controls recruited from the Parkinson's Progression Markers Initiative database. The patients were divided into two groups, PD with probable RBD and PD without probable RBD, according to the RBD screening questionnaire. Individual structural network of brain was constructed based on deterministic fiber tracking and analyses were performed using (...) graph theory. Differences in global and nodal topological properties were analyzed among the three groups. After that, post hoc analyses were performed to explore further differences. Finally, correlations between significant different properties and RBDSQ scores were analyzed in PD-pRBD group.ResultsAll three groups presented small-world organization. PD-pRBD patients exhibited diminished global efficiency and increased shortest path length compared with PD-npRBD patients and HCs. In nodal property analyses, compared with HCs, the brain regions of the PD-pRBD group with changed nodal efficiency were widely distributed mainly in neocortical and paralimbic regions. While compared with PD-npRBD group, only increased Ne in right insula, left middle frontal gyrus, and decreased Ne in left temporal pole were discovered. In addition, significant correlations between Ne in related brain regions and RDBSQ scores were detected in PD-pRBD patients.ConclusionsPD-pRBD patients showed disrupted topological organization of white matter in the whole brain. The altered Ne of right insula, left temporal pole and left middle frontal gyrus may play a key role in the pathogenesis of PD-RBD. (shrink)

This chapter contains section titled: The Structure of Knowledge Safety.

This paper examines tracer techniques in neuroscience, which are used to identify neural connections in the brain and nervous system. These connections capture a type of “structural connectivity” that is expected to inform our understanding of the functional nature of these tissues. This is due to the fact that neural connectivity constrains the flow of signal propagation, which is a type of causal process in neurons. This work explores how tracers are used to identify causal information, what standards they are (...) expected to meet, the forms of causal information they provide, and how an analysis of these techniques contributes to the philosophical literature, in particular, the literature on mark transmission and mechanistic accounts of causation. (shrink)

The tumor microenvironment (TME) plays a pivotal role in the behavior and development of solid tumors as well as shaping the immune response against them. As the tumor cells proliferate, the space they occupy and their physical interactions with the surrounding tissue increases. The growing tumor tissue becomes a complex dynamic structure, containing connective tissue, vascular structures, and extracellular matrix (ECM) that facilitates stimulation, oxygenation, and nutrition, necessary for its fast growth. Mechanical cues such as (...) stiffness, solid stress, interstitial fluid pressure (IFP), matrix density, and microarchitecture influence cellular functions and ultimately tumor progression and metastasis. In this fight, our body is equipped with T cells as its spearhead against tumors. However, the altered biochemical and mechanical environment of the tumor niche affects T cell efficacy and leads to their exhaustion. Understanding the mechanobiological properties of the TME and their effects on T cells is key for developing novel adoptive tumor immunotherapies. (shrink)

Brain structural covariance network can delineate the brain synchronized alterations in a long-range time period. It has been used in the research of cognition or neuropsychiatric disorders. Recently, causal analysis of structural covariance network, winner-take-all and cortex–subcortex covariance network, and modulation analysis of structural covariance network have expended the technology breadth of SCN. However, the lack of user-friendly software limited the further application of SCN for the research. In this work, we developed the graphical user interface toolkit of brain structural (...) covariance connectivity based on MATLAB platform. The software contained the analysis of SCN, CaSCN, MOD-SCN, and WTA-CSSCN. Also, the group comparison and result-showing modules were included in the software. Furthermore, a simple showing of demo dataset was presented in the work. We hope that the toolkit could help the researchers, especially clinical researchers, to do the brain covariance connectivity analysis in further work more easily. (shrink)

Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan and brain (...) shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation with various neuroimaging modalities has not yet been reported.Case Report: A 42-year-old left-handed man had increased intracranial pressure, left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function was performed, combined with magnetic resonance imaging -based tractography reconstruction of 6 neural tracts and resting-state functional MRI connectivity of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome.Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery. (shrink)

This paper investigates whether philanthropic giving decisions and amount of charitable giving are related to firms’ political connections and ownership type. To this end, Chinese firms listed on either the Shenzhen or Shanghai stock exchange between 2004 and 2011 are examined, where government interference in the business sector is prevalent, state ownership structure is dominant, and corporate political connections prevail. Our analyses show a significant and positive relationship between political connections and the likelihood and extent of firm contributions; a (...) significant and negative relationship between state ownership and extent of firm contributions; and a stronger relationship between political connections and corporate philanthropy in non-state-owned firms. These findings with regard to the relationship between corporate giving, political connections, and ownership type have important implications for understanding corporate giving behavior in China and in emerging markets in general. (shrink)

This open access book explains how leading business organizations attempt to achieve the responsible and ethical use of artificial intelligence (AI) and other advanced information technologies. These technologies can produce tremendous insights and benefits. But they can also invade privacy, perpetuate bias, and otherwise injure people and society. To use these technologies successfully, organizations need to implement them responsibly and ethically. The question is: how to do this? Data ethics management, and this book, provide some answers. -/- The authors interviewed (...) and surveyed data ethics managers at leading companies. They asked why these experts see data ethics as important and how they seek to achieve it. This book conveys the results of that research on a concise, accessible way. -/- Much of the existing writing on data and AI ethics focuses either on macro-level ethical principles, or on micro-level product design and tooling. The interviews showed that companies need a third component: data ethics management. This third element consists of the management structures, processes, training and substantive benchmarks that companies use to operationalize their high-level ethical principles and to guide and hold accountable their developers. Data ethics management is the connective tissue makes ethical principles real. It is the focus of this book. -/- This book should be of use to organizations that wish to improve their own data ethics management efforts, legislators and policymakers who hope to build on existing management practices, scholars who study beyond compliance business behavior, and members of the public who want to understand better the threats that AI poses and how to reduce them. (shrink)

The cerebral cortex is a rich and diverse structure that is the basis of intelligent behavior. One of the deepest mysteries of the function of cortex is that neural processing times are only about one hundred times as fast as the fastest response times for complex behavior. At the very least, this would seem to indicate that the cortex does massive amounts of parallel computation.This paper explores the hypothesis that an important part of the cortex can be modeled as (...) a connectionist computer that is especially suited for parallel problem solving. The connectionist computer uses a special representation, termed value unit encoding, that represents small subsets of parameters in a way that allows parallel access to many different parameter values. This computer can be thought of as computing hierarchies of sensorimotor invariants. The neural substrate can be interpreted as a commitment to data structures and algorithms that compute invariants fast enough to explain the behavioral response times. A detailed consideration of this model has several implications for the underlying anatomy and physiology. (shrink)

Whitehead, in his famous book "Process and Reality", proposed a definition of point assuming the concepts of “region” and “connection relation” as primitive. Several years after and independently Grzegorczyk, in a brief but very interesting paper proposed another definition of point in a system in which the inclusion relation and the relation of being separated were assumed as primitive. In this paper we compare their definitions and we show that, under rather natural assumptions, they coincide.

The work is concerned with the so called display property of display logic. The motivation behind it is discussed and challenged. It is shown using one display calculus for intuitionistic logic as an example that the display property can be abandoned without losing subformula, cut elimination and completeness properties in such a way that results in additional expressive power of the system. This is done by disentangling structural connectives so that they are no longer context-sensitive. A recipe for characterizing structural (...) extensions of display calculi is provided. (shrink)

Type 2 diabetes mellitus is associated with cognitive impairment in many domains. There are several pieces of evidence that changes in neuronal neuropathies and metabolism have been observed in T2DM. Structural and functional MRI shows that abnormal connections and synchronization occur in T2DM brain circuits and related networks. Neuroplasticity and energy metabolism appear to be principal effector systems, which may be related to amyloid beta deposition, although there is no unified explanation that includes the complex etiology of T2DM with cognitive (...) impairment. Herein, we assume that cognitive impairment in diabetes may lead to abnormalities in neuroplasticity and energy metabolism in the brain, and those reflected to MRI structural connectivity and functional connectivity, respectively. (shrink)

Open peer commentary on the article “Radical Constructivist Structural Design Education for Large Cohorts of Chinese Learners” by Christiane M. Herr. Upshot: In the target article, Christiane Herr offers an insightful characterization of how von Glasersfeld’s radical constructivism can be implemented in structural design education in architecture. In this commentary, I articulate possible connections between research on problem solving and problem posing in mathematics education and design processes in structural design education as described in the target article.

Marilyn Strathern’s arguments against the possibility of feminist research bringing about a paradigm shift in social anthropology have led to a number of responses. Regarding one argument she presents, her own writings suggest a response: the argument that feminist research cannot bring about such a shift, because it is only concerned with part of society. A foray into the history of British social anthropology is of value for appreciating this argument and the response.

Although the language-related fiber pathways in the human brain, such as the superior longitudinal fasciculus and arcuate fasciculus, are already well-known, understanding more sophisticated cortical regions connected by the fiber tracts is essential to scrutinize the structural connectivity of language circuits. With the regions of interest that were selected based on the Brainnetome atlas, the fiber orientation distribution estimation method for tractography was used to produce further elaborate connectivity information. The results indicated that both fiber bundles had two distinct connections (...) with the prefrontal cortex. The SLF-II and dorsal AF are mainly connected to the rostrodorsal part of the inferior parietal cortex and lateral part of the fusiform gyrus with the inferior frontal junction, respectively. In contrast, the SLF-III and ventral AF were primarily linked to the anterior part of the supramarginal gyrus and superior part of the temporal cortex with the inferior frontal cortex, including the Broca's area. Moreover, the IFJ in the PFC, which has rarely been emphasized as a language-related subregion, also had the strongest connectivity with the previously known language-related subregions among the PFC; consequently, we proposed that these specific regions are interconnected via the SLF and AF within the PFC, IPC, and temporal cortex as language-related circuitry. (shrink)

We give an example of a structure equation image on the real line, and a manifold M definable in equation image, such that M is definably connected but is not connected.

In May 2021, Royal Dutch Shell was ordered by the Hague District Court to significantly reduce its CO2 emissions. This ruling is unprecedented in that it attributes the responsibility for mitigating climate change directly to a specific corporate emitter. Shell neither directly causes climate change alone nor can alleviate it by itself; therefore, what grounds this responsibility attribution? I maintain that this question can be answered via Young’s social connection model of responsibility for justice. I defend two claims: First, I (...) argue that the model explains Shell’s connection to climate change and that this relationship grounds Shell’s responsibility. Second, by identifying a way in which the social connection model could be applied to corporations in legal practice, I further develop Young’s model. I question Young’s distinction between political and legal responsibility for justice and propose that courts could mediate citizens’ actions regarding political responsibilities. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Resisting Structural Evil: Love as Ecological-Economic Vocation by Cynthia Moe-LobedaKiara A. JorgensonReview of Resisting Structural Evil: Love as Ecological-Economic Vocation CYNTHIA MOE-LOBEDA Minneapolis: Fortress Press, 2013. 309 pp. $22.00The factors that have contributed to today’s perilous global economy and ecology originate in structures that predate recent implosions of international banks or measurements of rising climates. These structures—systemic and social while also personal—are the focus of Moe-Lobeda’s work, Resisting (...) Structural Evil: Love as Ecological-Economic Vocation. Convinced that sin and violence is “uncreating” the beauty of God’s interdependent community and can only be countered and alleviated by a moral vision structured around “justice-seeking love,” Moe-Lobeda provides a compelling theological critique and reconstruction of the Christian concept of love by way of a fresh retrieval of the classical Christian doctrine of vocation.The book’s argument consists of a tapestry of sobering statistics, theological analysis, and narrative prose. Early on Moe-Lobeda takes great care to explain how the moral crises of today relate to the embedded social structures of yesterday. Here her attention to the globalization of economies and subsequent ecological injustice is particularly helpful since few contemporary texts make explicit this critical connection. In a chapter titled “Countering Moral Oblivion” she also devotes attention to why seemingly good people, particularly good Christians, passively and ignorantly participate in systems of oppressive power. This portion of her book, coupled with her discussion of how Christian theology can be a resource of hope, is empowering and particularly attentive to the role of biblical theology in the ecological conversation. Unlike many other theoretical books on the topic, Moe-Lobeda’s book can be appropriated as a tool for lifestyle appraisal useful to the academician, pastor, and lay reader alike. Indeed, Moe-Lobeda can evoke discomfort with her compelling vision and challenging call for a change in our current practices.Pivoting her argument on the promise of hope, the second half of Resisting Structural Evil discusses what can and must be realized. And it is here that Moe-Lobeda’s voice makes a contribution not only to Christian ecological ethics but also to Christian social ethics at large. Vocation, she argues, encompasses more than what traditional renderings of vocare have sought to connote. The human call to life is a call to love in compassion and justice both the neighbor [End Page 208] and the self, and must be made manifest in the public sphere. What is more, one must fulfill one’s vocation not only for the sake of the human other but also for the benefit of the oikos (household) present within all economic and ecological communities. To this end, Moe-Lobeda’s attention to love as vocation uniquely characterizes her approach to ecological ethics, thereby transcending traditional deontolological or teleological classifications. Unique within Protestant work on ecological ethics, Resisting Structural Evil provides a fresh depiction of character ethics wherein the pursuit of moral aptitude is fundamentally rooted in biotic community.This very strength may also foster some critique since Moe-Lobeda’s schema is so thoroughly corporate in scope that it affords little time and attention to what some virtue and character ethicists would call the inward journey. Yet Moe-Lobeda, aligned with the liberal and feminist traditions from which she hails, views love and power as inseparable. “What is needed,” she argues, “is a realization that power without love is reckless and abusive and that love without power is sentimental and anemic” (169). Hence, on a very fundamental level Resisting Structural Evil is a book arguing for a radically new paradigm, one where the enormity of today’s crises is met with an equally comprehensive dose of transformative loving power.Kiara A. JorgensonLuther SeminaryCopyright © 2015 Society of Christian Ethics... (shrink)

. The connection presented in this paper mirror-links two metamathematical structures, the finitary closure operators, and the compact consistency properties, in such a way that a specification of one structure induces a provably equivalent specification of the other.

Inspired by the application of CycleGAN networks to the image style conversion problem Zhu et al., this paper proposes an end-to-end network, DefogNet, for solving the single-image dehazing problem, treating the image dehazing problem as a style conversion problem from a fogged image to a nonfogged image, without the need to estimate a priori information from an atmospheric scattering model. DefogNet improves on CycleGAN by adding a cross-layer connection structure in the generator to enhance the network’s multiscale feature extraction (...) capability. The loss function was redesigned to add detail perception loss and color perception loss to improve the quality of texture information recovery and produce better fog-free images. In this paper, the novel Defog-SN algorithm is presented. This algorithm adds a spectral normalization layer to the discriminator’s convolution layer to make the discriminant network conform to a 1-Lipschitz continuum and further improve the model’s stability. In this study, the experimental process is completed based on the O-HAZE, I-HAZE, and RESIDE datasets. The dehazing results show that the method outperforms traditional methods in terms of PSNR and SSIM on synthetic datasets and Avegrad and Entropy on naturalistic images. (shrink)

Child trauma plays an important role in the etiology of Bordeline Personality Disorder. Of all traumas, sexual trauma is the most common, severe and most associated with receiving a BPD diagnosis when adult. Etiologic models posit sexual abuse as a prognostic factor in BPD. Here we apply machine learning using Multiple Kernel Regression to the Magnetic Resonance Structural Images of 20 BPD and 13 healthy control to see whether their brain predicts five sources of traumas: sex abuse, emotion neglect, emotional (...) abuse, physical neglect, physical abuse. We also applied the same analysis to predict symptom severity in five domains: affective, cognitive, impulsivity, interpersonal for BPD patients only. Results indicate that CTQ sexual trauma is predicted by a set of areas including the amygdala, the Heschl area, the Caudate, the Putamen, and portions of the Cerebellum in BPD patients only. Importantly, interpersonal problems only in BPD patients were predicted by a set of areas including temporal lobe and cerebellar regions. Notably, sexual trauma and interpersonal problems were not predicted by structural features in matched healthy controls. This finding may help elucidate the brain circuit affected by traumatic experiences and connected with interpersonal problems BPD suffer from. (shrink)

It has been claimed that contracting connectivesContracting connective are conditionalsConditional. Our modest aim here is to show that the conditional-like features of a contracting connectiveContracting connective depend on the defining features of the conditionalConditional in a particular logic, yes, but they also depend on the underlying notion of logical consequence and the structure of the collection of truth values. More concretely, we will show that under P-consequenceP-consequence and suitable satisfiability conditions for the conditionalConditional, conjunctionsConjunction are contracting connectivesContracting (...) connective for some logics without thereby being conditional-ish. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Colin Falck STRUCTURE AND INTUITION I KANT'S ANSWER, in his Critique ofPure Reason, to the Humean problem that there seemed to be no way of explaining the principle of our experiential unity, of what it is that holds us together as experiencing selves or consciousnesses, was to argue that it was language itselfwhich underlay the whole possibility of our self-consciousness and of our consciousness of a world of (...) objects around us. Experience would not be possible without a unified consciousness, and a unified consciousness is only possible for us because of the use which we make of certain concepts of"the objects of experience." ' Kant argues at some length that there can be no perceptual experience without conceptual language, and in particular without our use of what he calls the a priori "categories" or "pure concepts of understanding " (CPR, B. 102 et seq.). (A similar, but more sophisticated, argument about the necessary dependence of perceptual experience on conceptual language was developed later by Wittgenstein.) Saussure, in his Course in General Linguistics,2 though never it seems in a fully aware or explicit way, founds his entire argument on this Kantian conclusion when he remarks that the notion "that ready-made ideas exist before words" is "open to criticism at several points" (p. 65), and goes on to elaborate a view of linguistic meanings as based in the relationships which hold between linguistic terms or units themselves rather than in any kind of "namingprocess " or "correspondence" between individual words and the things that they name (pp. 65, 111-18). A difficulty which faces, and which (unless certain amendments are made) must ultimately invalidate, the account of experience and language which Kant sets out in the Critique of Pure Reason is that the Kantian experiencing self, even though it is a concept-using and therefore perhaps 184 Colin Falck185 logically plausible subject, is at the same time also a disembodied subject. To that extent it is open to some of the same objections that can be brought against Descartes's conception of the thinking subject, or ego, as the foundation of all our experiencing. The problem which Kant did not recognize is that there could be no way for us to know about the existence of other experiencing agents, or therefore to have any awareness of the distinction between ourselves and other selves, if we could not in fact see the putative other person as an experiencing and thinking consciousness. To see another person in this way it must be possible to see him as, and it must be essential to his identity that he should really be, an embodied consciousness, rather than merely a Cartesian disembodied ego or (since the same arguments must apply) a Kantian disembodied concept-using self. (Without being embodied or located, there is no way for the Kantian self to be a perceiving agent with an identity which endures through time: the mere "unity of self-consciousness" which Kant offers us does not in fact give us any solution to Hume's problem at all.) The body, we might say, is that realm in which, or through which, we have our contact with, and therefore our awareness of, other consciousnesses — and at the same time, by contrast, our awareness of our own selfhood or consciousness as well.3 We cannot see another person only as "external" behavior, but must necessarily see his behavior as already inhabited by mind or spirit. Were this not so, there would be no way, to use the Kantian or "transcendental" turn of argument, for us to have the kind of experience which we indisputably do have. Ultimately therefore, if we reflect on the deficiencies of the Kantian position in the "disembodied" form in which Kant himself sets it out, we shall be obliged to recognize that the only kind of concept which will make the required connections between the "inside" and the "outside" of human behavior — a logical gap which seems all too easily to open up beneath us in this area — will be some kind of concept oí sympathy, or of preconscious imitative identification, which, by bridging the divide between "internally experienced" consciousness and "externally observable" movement, makes it... (shrink)

This article is concerned with pragmatic connectives and their uses in discursive argumentation. Three approaches to pragmatic connectives will be presented: (1) argumentation theory, which implies a conception of pragmatics integrated within semantics, and a specific type of argumentative rules, called ‘topoi’; (2) discourse structure theory, which associates a function in the structuring of discourse sequences to pragmatic connectives; (3) relevance theory, which constitutes a cognitive pragmatic theory, in which no specific principle is associated to linguistic items. However, two (...) main functions to pragmatic connectives can be proposed: the facilitation of inferences, and the access to relevance. The final purpose of this article is to indicate how argumentative effects in discourse can be explained in a cognitively-based pragmatic theory. (shrink)

BACKGROUND: Alzheimer's disease is intimately tied to amyloid-beta peptide. Extraneuronal brain plaques consisting primarily of Abeta aggregates are a hallmark of AD. Intraneuronal Abeta subunits are strongly implicated in disease progression. Protein sequence mutations of the Abeta precursor protein account for a small proportion of AD cases, suggesting that regulation of the associated gene may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or "proximal regulatory element" , at -76/-47, from the (...) +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. RESULTS: EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 , nm23 nucleoside diphosphate kinase/metastatic inhibitory protein , and specificity protein 1 . These sites crossed a known single nucleotide polymorphism . EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. CONCLUSIONS: We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also interacts with the integrins. These proteins are connected to vital cellular and neurological functions. In addition, the transcription factor PuF is a known inhibitor of metastasis and regulates cell growth during development. Given that APP is a known cell adhesion protein and ferroxidase, this suggests biochemical links among cell signaling, the cell cycle, iron metabolism in cancer, and AD in the context of overall aging. (shrink)

The Body as Gift, Resource, and Commodity, edited by Martin Gunnarson and Fredrik Svenaeus, is a volume containing 11 research pieces about organ transplants and organ trade in current times, and is the outcome of a research project at the Centre for Studies in Practical Knowledge, Södertörns University in Stockholm. The main contributors include a philosopher, a historian, and three ethnologists, assisted by medical researchers and physicians and other scholars from the Baltic region. As such, the range of focus is (...) generally limited to the prevailing practices in that region, although their connections with practices in other parts of the world are discussed where directly relevant.The authors’ aim, as mentioned in the introduction of the book, is to add to the growth of knowledge and reflection in the field of reference and thus help to build sound political judgment and policies on organ, tissue, and cell donation, both in view of the need to save lives and their impac .. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:120 HISTORY OF PHILOSOPHY weapons," the emotive meanings of propaganda (p. 168). Thus his main distinctions between understanding and will, science and art, knowing and doing, civil and penal, were repeatedly blurred as his tactics shifted. Bentham's originality, says Mack, "lay just here, in putting moral insights to use by first incorporating them in a systematic analytic structure." Yet he "never fully explained what he intended to include (...) under a 'logic of the will.' He began with individuals, their immediate pleasures and pains, and a Utilitarian rationale or consideration of consequences..." but the essential connective tissues were never sufficiently supplied (pp. 160-161). But at least the logic of the will and Bentham's bitter frustrations as a reformer combined to make him a radical democrat by 1790, and not, as the author clearly and for the first time demonstrates, because of the influence of James Mill some twenty years later. With a wealth of detail the author accompanies Bentham just beyond the mid-point of his odyssey, and fully justifies her admiration for what he attempted to do. She recognizes the obvious "gap between his ambition and his achievement," to which must be added the distance between his psychology and sociology and ours. Many of the questions he raised are still with us, and have even been sharpened, as the late David Baumgardt pointed out, by the logical positivists and the emotivists. In today's discussions, as he indicates, we are often confronted with a choice between but two alternatives: uncritical normative ethics and ethical or non-ethical psychology. Bentham offers at least the possibility of "basing ethics critically upon psychological observations." And Stevenson speaks of attitudes which can be "supported" by some "reasoned argument " (David Baumgardt, Bentham and the Ethics oI Today [Princeton, New Jersey: 1952], pp. 137-150). Nothing in this excellent beginning leads the reader to expect the second volume to portray the completion by Bentham of the majestic structures which he planned and replanned. But a case has been made for a reassessment of Bentham as an adventurer, if not as a builder in philosophy, so that one looks forward to the next installment of his odyssey. HAROLD A. LARRABEE Union College,Schenectady,New York Positives Antichristentum: Nietzsches Christusbild im Brennpunkt nachchristlicher Anthropologie. By Hermann Wein. (The Hague: Martinus Nijhoff, 1962. Pp. 114. 9.50 G.) For understandable reasons, a definitive study of the philosophy of Nietzsche has never been written-and may never be written. Nietzsche's predilection for dialectics, the restless to-and-fro with which he at once affirms and negates virtually every cultural and intellectual phenomenon of the western world, including some products of his own creative imagination, is the despair even of those commentators who would heed his warning that there is no fixed center to his thought. Thus we have had interpretations of Nietzsche as atheist, as secular eschatologist, as nihilist, as cultural relativist, as Dionysian yea-sayer, as Darwinian eugenicist, and the like--none of them altogether mistaken, all of them, singly and collectively, beset by a frustrating one-sidedness. It would be too much to say that Professor Wein has succeeded where all others have [ailed. But he has managed to present more of a "whole" Nietzsche than have his prede- BOOK REVIEWS 121 r He has honored his own sound methodological precept that "only in a farspanning synopsis of what constitutes the aphoristically dispersed Nietzschean corpus does the contrapuntal order of this open, nonsystematic philosophy become apparent" (p. as). Nietzsche, Professor Wein insists, was not an out-and-out nihilist. But in the face of his wholesale negations of what the West has traditionally understood by and accepted as real, true, and valuable, what was left for Nietzsche to affirm? By way of answer, Wein devotes more than half of his book to a multiperspectival exegesis of Nietzsche's briefest and best-known pronouncement: "God is dead." In the first place, the pronouncement is an historical report. "God," a shorthand expression for the hierarchized meanings and values developed by the Judeo-Christian tradition, is all but extinct. Thus for Nietzsche the contemporary era is the epoch of the ascendancy of nihilism. In the second place... (shrink)

An exploration of ground’s connections to structure (joint-carving, naturalness). The notion of structure is often invoked in connection to ground, because grounding is understood to impose constraints on the ‘structure of reality’. There is another, technical sense of structure, sometimes captured with reference to the notion of ‘joint-carving’. Both of these senses of structure as well as their potential connections are discussed.

Linguistic structures have recently started to attract attention from economists as determinants of economic phenomena. This paper provides the first comprehensive review of this nascent literature and its achievements so far. First, we explore the complex connections between language, culture, thought and behaviour. Then, we summarize the empirical evidence on the relationship between linguistic structures and economic and social outcomes. We follow up with a discussion of data, empirical design and identification. The paper concludes by discussing implications for future research (...) and policy. (shrink)

This paper describes the topological aspect of a logic-based, artificial intelligence approach to formalising the qualitative description of spatial properties and relations, and reasoning about those properties and relations. This approach, known as RCC theory, has been under development for several years at the University of Leeds. The main rationale for this project is that qualitative descriptions of spatial properties and relationships, and qualitative spatial reasoning, are of fundamental importance in human thinking about the world: even where quantitative spatial data (...) are most important, they must be attached to the components of a perceived spatial structure if we are to make use of them. RCC theory covers other qualitative aspects of spatial description and reasoning, but the topological properties and relations of spatially extended entities are fundamental to our work. The topological formalisms used by mathematicians are, in general, not well suited to the task of formalising the kinds of ‘common-sense’ or ‘everyday’ qualitative spatial description and reasoning which are our primary interest. Nevertheless, we must come to grips with the concepts of topology as practised by mathematicians if we are not to risk constantly ‘reinventing wheels’. (shrink)

High-level improvising musicians master idiosyncratic gesture vocabularies that allow them to express themselves in unique ways. The full use of such vocabularies is nevertheless challenged when improvisers incorporate electronics in their performances. To control electronic sounds and effects, they typically use commercial interfaces whose physicality is likely to limit their freedom of movement. Based on Jim Black's descriptions of his ideal digital musical instrument, embodied improvisation gestures, and stage performance constraints, we develop the concept of a modular wearable MIDI interface (...) to closely meet the needs of professional improvisers, rather than proposing a new generic instrument that would require substantial practice to adapt improvisational techniques already acquired. Our research draws upon different bodies of knowledge, from theoretical principles on collaboration and embodiment to wearable interface design, in order to create a digital vest called Track It, Zip It that features two innovative on-body sensors. Allowing for sound control, these sensors are seamlessly integrated with Black's improvisational gesture vocabulary. We then detail the design process of three TIZI prototypes structured by the outcomes of a performance test with Black, a public performance by a novice improviser during the 2017 International Guthman Musical Instrument Competition, and measurements of sensor responses. After commenting on the strengths and weaknesses of the final TIZI prototype, we discuss how our interdisciplinary and collective process involving a world-class improviser at the very center of the design process can provide recommendations to designers who wish to create interfaces better adapted to high-level performers. Finally, we present our goals for the future creation of a wireless version of the vest for a female body based on Diana Policarpo's artistic vision. (shrink)

It has long been assumed that the architectural proteins of chromatin (the histones, for example) are unrelated to their functional proteins (transcription factors, polymerases, etc). New studies(1,2)drastically change this perspective. It appears that a portion of the general transcription initiation complex TFIID is made up of proteins that not only carry marked sequence and structural resemblances to the core histones of the nucleosome, but also form an octameric complex similar to the histone octamer. This can now be seen as part (...) of a general pattern of continuity among structural and functional chromatin proteins. (shrink)

A philosophically useful account of social structure must accommodate the fact that social structures play an important role in structural explanation. But what is a structural explanation? How do structural explanations function in the social sciences? This paper offers a way of thinking about structural explanation and sketches an account of social structure that connects social structures with structural explanation.

Neuroscience research has shown that meditation practices have effects on brain structure and function. However, few studies have combined information on the effects on structure and function in the same sample. Long-term daily meditation practice produces repeated activity of specific brain networks over years of practice, which may induce lasting structural and functional connectivity changes within relevant circuits. The aim of our study was therefore to identify differences in FC during the resting state between 23 Sahaja Yoga Meditation (...) experts and 23 healthy participants without meditation experience. Seed-based FC analysis was performed departing from voxels that had shown structural differences between these same participants. The contrast of connectivity maps yielded that meditators showed increased FC between the left ventrolateral prefrontal cortex and the right dorsolateral prefrontal cortex but reduced FC between the left insula and the bilateral mid-cingulate as well as between the right angular gyrus and the bilateral precuneus/cuneus cortices. It thus appears that long-term meditation practice increases direct FC between ventral and dorsal frontal regions within brain networks related to attention and cognitive control and decreases FC between regions of these networks and areas of the default mode network. (shrink)

Structural proof theory is a branch of logic that studies the general structure and properties of logical and mathematical proofs. This book is both a concise introduction to the central results and methods of structural proof theory, and a work of research that will be of interest to specialists. The book is designed to be used by students of philosophy, mathematics and computer science. The book contains a wealth of results on proof-theoretical systems, including extensions of such systems from (...) logic to mathematics, and on the connection between the two main forms of structural proof theory - natural deduction and sequent calculus. The authors emphasize the computational content of logical results. A special feature of the volume is a computerized system for developing proofs interactively, downloadable from the web and regularly updated. (shrink)

Structural realism is considered by many realists and antirealists alike as the most defensible form of scientific realism. There are now many forms of structural realism and an extensive literature about them. There are interesting connections with debates in metaphysics, philosophy of physics and philosophy of mathematics. This entry is intended to be a comprehensive survey of the field.

We are conscious beings who think, understand, feel and perceive. We are also material beings composed out of ordinary material stuff. Determining the precise connections between the psychological and the material remains problematic. The harmonia theory is one of the first attempts to frame this as a problem about composite objects. The theory itself is simple: the soul is the harmonia of the material parts of the body. But what a harmonia is and what the theory amounts to are matters (...) of much dispute. I argue that a harmonia is best understood as the structure of the body's material parts. Plato introduces the theory in the Phaedo, and Aristotle mentions it in On the Soul. In both instances it is roundly criticized. Given that Plato thinks the soul is independent of the body, it is not surprising that he rejects the harmonia theory. However, he has been described as "extraordinarily obtuse" for arguing against the view, since doing so seems to undermine his arguments for a tripartite soul. Aristotle's rejection has been thought equally perplexing, since his own positive view looks very much like a version of the harmonia theory. Looking closely at the harmonia theory helps clarify persistent misunderstandings of the view and the reasons Plato and Aristotle reject it. This avenue offers insight into Plato's and Aristotle's positive theories about the soul and its relation to matter. In addition, their rejections of the theory shed light on how they understand the relation between parts and wholes. The problems lying behind the ancient debate about the harmonia theory are not just historically significant, but also resonate with contemporary discussions about material composition and the metaphysics of mind. Plato articulates a version of the harmonia theory which is perhaps the first expression of a supervenience thesis about the mental, but the precise sort of supervenience at issue hasn't been well understood. But most importantly, whether wholes and souls are causally relevant and whether conscious beings are mereologically simple are issues at the heart of the debate, both ancient and modern. (shrink)

Methylation of DNA plays an important role in the control of gene expression in higher eukaryotes. This is largely achieved by the packaging of methylated DNA into chromatin structures that are inaccessible to transcription factors and other proteins. Methylation involves the addition of a methyl group to the 5‐position of the cytosine base in DNA, a reaction catalysed by a DNA (cytosine‐5) methyltransferase. This reaction occurs in nuclear replication foci where the chromatin structure is loosened for replication, thereby allowing (...) access to methyltransferases. Partly as a result of their recognising the presence of a methylcytosine on the parental strand following replication, these large enzymes are able to maintain the distribution of methyl groups along the DNA of somatic cells and, thereby, maintain tissue‐specific patterns of gene expression. (shrink)

Regularization may be used as an alternative to dimensionality reduction when the number of variables in a model is much larger than the number of available observations. In a recent study from our group regularized regression was employed to quantify brain functional connectivity in a sample of healthy controls using a brain parcellation and resting state fMRI images. Here regularization is applied to evaluate resting state connectivity abnormalities at the voxel level in a sample of patients with schizophrenia. Specifically, ridge (...) regression is implemented with different degrees of regularization. Results are compared to those delivered by the weighted global brain connectivity method, which is based on averaged bivariate correlations and from the non-redundant connectivity method, a dimensionality reduction approach that applies supervised principal component regressions. Ridge regression is able to detect a larger set of abnormally connected regions than both GBC and NRC methods, including schizophrenia related connectivity reductions in fronto-medial, somatosensory and occipital structures. Due to its multivariate nature, the proposed method is much more sensitive to group abnormalities than the GBC, but it also outperforms the NRC, which is multivariate too. Voxel based regularized regression is a simple and sensitive alternative for quantifying brain functional connectivity. (shrink)

A three‐tiered legal structure of the substances constitutive of human beings can accommodate property rights in new products created by the investment of labor in human tissue.

This paper is a continuation of investigations on Galois connections from [1], [3], [10]. It is a continuation of [2]. We have shown many results that link properties of a given closure space with that of the dual space. For example: for every -disjunctive closure space X the dual closure space is topological iff the base of X generated by this dual space consists of the -prime sets in X (Theorem 2). Moreover the characterizations of the satisfiability relation for classical (...) logic are shown. Roughly speaking our main result here is the following: a satisfiability relation in a logic L with, a countable language is a fragment of the classical one iff the compactness theorem for L holds (Theorems 3–8). (shrink)

Ontic structural realism constitutes a promising take on scientific realism, one that avoids the well‐known issues that realist stances have with underdetermination and theory change. In its most radical versions, ontic structural realism proposes a type of eliminativism about theoretical entities, ascribing ontological commitment only to the structures, and not to the objects appearing in our theories. More moderate versions of ontic structural realism have also been proposed, allowing for ‘thin’ objects in the ontology. This work connects these takes on (...) structural realism with the independent notion that there are two categorically different kinds of scientific theories, namely those that deal with interactions and those that deal with structural constraints – what are known as interaction and framework theories, respectively. By taking this classification seriously, one can arrive at a selective version of ontic structural realism which is better adapted to our scientific knowledge, in which eliminativist ontic structural realism constitutes a natural fit to framework theories, whereas the moderate version is connected to interaction theories. (shrink)

This paper explores the different identities adopted by connective tissue research at the University of Manchester during the second half of the 20th century. By looking at the long-term redefinition of a research programme, it sheds new light on the interactions between different and conflicting levels in the study of biomedicine, such as the local and the global, or the medical and the biological. It also addresses the gap in the literature between the first biomedical complexes after World (...) War II and the emergence of biotechnology. Connective tissue research in Manchester emerged as a field focused on new treatments for rheumatic diseases. During the 1950s and 60s, it absorbed a number of laboratory techniques from biology, namely cell culture and electron microscopy. The transformations in scientific policy during the late 70s and the migration of Manchester researchers to the US led them to adopt recombinant DNA methods, which were borrowed from human genetics. This resulted in the emergence of cell matrix biology, a new field which had one of its reference centres in Manchester. The Manchester story shows the potential of detailed and chronologically wide local studies of patterns of work to understand the mechanisms by which new biomedical tools and institutions interact with long-standing problems and existing affiliations. (shrink)

The theory of mind debate has reached a “hybrid consensus” concerning the status of theory-theory and simulation-theory. Extant hybrid models either specify co-dependency and implementation relations, or distribute mentalizing tasks according to folk-psychological categories. By relying on a non-developmental framework these models fail to capture the central connection between simulation and theory. I propose a “dynamic” hybrid that is informed by recent work on the nature of similarity cognition. I claim that Gentner’s model of structure-mapping allows us to understand (...) simulation as a process in which psychological representations are aligned, causing the spontaneous abstraction of theoretical generalizations about the psychological domain. (shrink)

Some authors argue that phenomenal unity can be grounded in the attentional structure of consciousness, which endows conscious states with at least a foreground and a background. Accordingly, the phenomenal character of part of a conscious state comprises a content aspect and a structural aspect. This view presents the concern that such a structure does not bring about phenomenal unity, but phenomenal segregation, since the background is separated from the foreground. I argue that attention can still lead to (...) a form of phenomenal unity that connects the foreground with the background. Experiencing oneself as controlling the focus of attention can, at least occasionally, bring about an experienced connection between the attentional foreground and the attentional background of a conscious experience. (shrink)

Ethical issues regarding research biobanks continue to be a topic of intense debate, especially issues of confidentiality, informed consent, and child participation. Although considerable empirical literature concerning research biobank ethics exists, very little information is available regarding the opinions of medical professionals doing genetics research from the Middle East, especially Arabic speaking countries. Ethical guidelines for research biobanks are critically needed as some countries in the Middle East are starting to establish national research biobanks. Islam is the dominant religion in (...) these countries, and it affects people’s behavior and influences their positions. Moreover, communities in these countries enjoy a set of customs, traditions and social norms, and have social and familial structures that must be taken into account when developing research policies. We interviewed 12 medical professionals from the Middle East currently working with stored tissue samples to document their opinions. We found general agreement. Participants’ primary concerns were similar to the views of researchers internationally. Since children tend to represent a high percentage of Middle Eastern populations, and because children’s bodies are not just small adult bodies, the interviewed professionals strongly believed that it is imperative to include children in biobank research. Participants generally believed that protecting confidentiality is socially very important and that informed consent/assent must be obtained from both adult and child participants. This study provides a starting point for additional studies. (shrink)