There is at present a widespread unease about the direction in which our technology is taking us, apparently against our will. Promising advances seem to carry with them unforeseen negative consequences, including damage to the environment and the reduction of work to the trivial mechanical repetition of actions which have no human meaning. However, attempts to design a better, human-centered technology--one that complements rather than rejects human skills--are all too often frustrated by the prevailing belief that "man is a machine," (...) and one, moreover, that compares badly in terms of performance and durability. This contentious and stimulating book offers a new approach, one that refutes four centuries of science based on strictly causal explanations. It shows that man and nature can be viewed as "machines with a purpose," and that the "purpose" can be the advancement of technology to the benefit and not the detriment of the human race and its environment. This fascinating work is accessible to a wide range of readers, scientists and nonspecialists alike. It will interest anyone concerned about the impact of technology and the way it is shaping our world. (shrink)

Scientific knowledge and mathematical analysis enter into engineering in an indispensable way, and their role will continually increase. But engineering contains elements of experience and judgment, of tacit knowledge, and regard for social considerations and the most effective way of using human labour. If we accept this element of ‘art’ in engineering, we should design our systems, not to reject human skill, but rather to cooperate with it and make it more protective.

In the paper, three propositions are put forward. First, that intellectual structures of wide scope commonly lead to conclusions which are ethically unacceptable; secondly that the ethically unacceptable consequences of science arise from one particular presupposition which it adopts, namely that of causality; thirdly, that causality is no essential part of science.

A nascent science in the sixteenth century rejected explanations in terms of purpose in favour of causality, and this bias has persisted and grown stronger. It has unfortunate consequences in areas where social and ethical considerations should prevail, and the paper describes a search extending over 20 years for a way in which these consequences could be avoided.

OBJECTIVE: How outside factors affect physician decision making remains an open question of vital importance. We sought to investigate the importance of various influences on physician decision making when clinical guidelines differ from patient preference. -/- METHODS: An online survey asking 469 primary care providers (PCPs) across four practice sites whether they would order magnetic resonance imaging for a patient with uncomplicated back pain. Participants were randomized to one of four scenarios: a patient's preference for imaging (control), a patient's preference (...) plus a colleague's opinion against imaging (colleague), a patient's preference plus a professional society's recommendation against imaging (profession), or a patient's preference plus an accountable care organization's quality metric that measures physician use of imaging (ACO). Demographic information and the reasoning behind participants' decisions also were obtained. -/- RESULTS: A total of 168 PCPs completed the survey, yielding a 36% completion rate. A majority chose not to pursue imaging: control 68%, colleague 85%, profession 87%, and ACO 78%. Multivariate logistic regression revealed that participants were more likely not to order advanced imaging only when reminded of a professional society recommendation (P = 0.017). Regression also suggested that practice site exerted an effect on the primary outcome. Evidence-based medicine and clinical judgment were the most cited reasons for the decision. -/- CONCLUSIONS: Our results reinforce the potential to leverage professional societies to advance evidence-based medicine and reduce unnecessary testing. At the same time, practice site appeared to exert influence, suggesting that these recommendations must be part of local institutional culture to be effective. (shrink)

In a recent book, ‘Machines with a Purpose’, many of the unattractive features of our technology were traced to a view of the world which has predominated in science for nearly four hundred years. This is, that nature, and everything that it contains, operates causally and without purpose. To counter this view, an alternative, purposive view was developed. The paper gives a simple account of this development, of other related work, and of the underlying motivation.

If one interprets the ‘ecology of technology’ as the study of technology in relation to its environment, there are two important levels at which this study can be made. It is possible to consider the different environments in Europe, Japan and the USA, and look for the different technological influences which accompany them. At a more general level, one can look at those factors which are common to all three environments, and which are associated with generic similarities in the technology (...) of all three areas.The paper considers both aspects as they have been experienced in Europe in some attempts to develop a ‘human-centred technology’. (shrink)

O presente trabalho examina os aspectos históricos da extração do óleo de canela-sassafrás (Ocotea pretiosa Mez), rico em safrol, no Alto e Médio Vale do Itajaí, a partir de 1940, por iniciativa de Otto Grimm, no município de Rio do Sul. Apresenta-se o tema no contexto da memória química em Santa Catarina, e discutem-se os procedimentos utilizados, e principalmente os motivos que levaram tal indústria incipiente a não se converter em uma indústria de química fina. Para tanto, são apresentados alguns (...) dados pertinentes à química do safrol, indicando que tal indústria poderia ter evoluído, bem como os aspectos econômicos e sociais que, ao lado da proibição do corte da canela-sassafrás, levaram em 1990 à extinção definitiva dessa "química fina que poderia ter sido". (shrink)

Soluble components of Notch signalling can be applied to manipulate a central pathway essential for the development of metazoans and often deregulated in illnesses such as stroke, cancer or cardiovascular diseases. Commonly, the Notch cascade is inhibited by small compound inhibitors, which either block the proteolysis of Notch receptors by γ‐secretases or interfere with the transcriptional activity of the Notch intracellular domain. Specific antibodies can also be used to inhibit ligand‐induced activation of Notch receptors. Alternatively, naturally occurring endogenous inhibitors of (...) Notch signalling might offer a specific way to block receptor activation. Examples are the soluble variants of the canonical Notch ligand Jagged1 and the non‐canonical Notch ligand Dlk1, both deprived of their transmembrane regions upon ectodomain shedding, or the bona fide secreted molecule EGFL7. We present frequently used methods to decrease Notch signalling, and we discuss how soluble Notch inhibitors may be used to treat diseases. (shrink)

Work requirements are the centerpiece of HHS's Trump Administration strategy to undo the ACA expansion for low income working age adults. This article examines the June 29, 2018 trial court opinion in Stewart v. Azar which held that HHS's approval of Kentucky's Section 1115 work demonstration was “arbitrary and capricious.” The purpose of Medicaid is to provide health coverage and HHS may not ignore the loss of coverage that will result from a work requirement.

Der zweite Band der DSKE enthält Kierkegaards Journale und Aufzeichnungen aus den Jahren 1836-1846. Examensvorbereitungen, aber auch Materialien zum Frühwerk bilden die Kernstücke dieses Bandes. Von herausragender Bedeutung ist Journal JJ, das als Diskussionsforum und literarische Werkstatt parallel zum pseudonymen Werk angesehen werden kann; hinzu kommen Kierkegaards Reflexionen zur gescheiterten Verlobung mit Regine Olsen. DSKE 2 basiert auf der historisch-kritischen dänischen Neuausgabe und bietet die Übersetzung der Journale und Aufzeichnungen sowie die Kommentare in einem Band. Pluspunkte: die erste kritische deutsche (...) Edition der Journale Kierkegaards erste Komplettedition der Journale in Deutschland mit detaillierten Kommentaren. (shrink)

Hastings Center Report, Volume 52, Issue 1, Page 21-28, January/February 2022.

The mammalian immune system is a subject of great research interest because of its powerful information processing capabilities, namely, adaptivity. The adaptivity of the immune system is characterized by mainly two aspects, responsibility and diversity. The responsibility is a result of the response network of the immune system and the diversity is arise from gene rearrengement of the immune system. Recentry many artificial immune algorithms were devised by inspiring the adaptivity of the immune system. In terms of the two aspects (...) of the immune system, however, those artificial immune algorithms only utilize the responsibility using models of response and regulation networks in the immune system. This paper proposes a new scheme of artificial immune algorithm, called Rearrangement Immune Algorithm, in which the rearrengement of the immune system is utilized combining evolution of the gelmline with an optimization of genetic algorithms. We empirically shows the effectiveness of our new scheme, RIA, with applying the Rosenbrock function and an HP folding problem. (shrink)

Nearly 90 % of allegations of biomedical research misconduct in the United States are dismissed by responsible institutions without any faculty assessment or auditable record. Recently, members of the U.S. Congress have complained that the penalties for those against whom findings of research misconduct are made are too light and that too few grant funds associated with research misconduct have been recovered for use by other researchers and taxpayers. Here we discuss the laws that empower federal agencies that can oversee (...) investigations of biomedical research misconduct: the Office of Research Integrity and the Office of the Inspector General, both located within the Department of Health and Human Services. Research misconduct investigations pertaining to U.S. physical sciences funded through the National Science Foundation are overseen by the NSF’s OIG. While OIGs may provide some improvement over the ORI in the handling of research misconduct, we have found that a much more serious flaw exists which undermines an ability to conduct performance audits of the effectiveness by which allegations of research misconduct are handled in the United States. Specifically, sufficient data do not need to be retained by U.S. research institutions funded by HHS or NSF to allow effective audit of why allegations of research misconduct are dismissed before being seen by faculty inquiry or investigative committees. U.S. federal Generally Accepted Government Auditing Standards, if applied to the research misconduct oversight process, would allow a determination of whether the handling of allegations of biomedical research misconduct actually functions adequately, and if not, how it might be improved. In particular, we propose that independent, external peer review under GAGAS audit standards should be instituted without delay in assessing the performance of ORI, or any other similarly tasked federal agency, in handling allegations of research misconduct. (shrink)

Hedgehog (Hh) signaling is a widely studied signaling pathway because of its critical roles during development and in cell homeostasis. Vertebrate canonical and non‐canonical Hh signaling are typically assumed to be distinct and occur in different cellular compartments. While research has primarily focused on the canonical form of Hh signaling and its dependency on primary cilia – microtubule‐based signaling hubs – an extensive list of crucial functions mediated by non‐canonical Hh signaling has emerged. Moreover, amounting evidence indicates that canonical and (...) non‐canonical modes of Hh signaling are interlinked, and that they can overlap spatially, and in many cases interact functionally. Here, we discuss some of the many cellular effects of non‐canonical signaling and discuss new evidence indicating inter‐relationships with canonical signaling. We discuss how Smoothened (Smo), a key component of the Hh pathway, might coordinate such diverse downstream effects. Collectively, pursuit of questions such as those proposed here will aid in elucidating the full extent of Smo function in development and advance its use as a target for cancer therapeutics. (shrink)

Hedgehog (HH) signaling is a conserved pathway that drives developmental growth and is essential for the formation of most organs. The expression of HH target genes is regulated by a dual switch mechanism where GLI proteins function as bifunctional transcriptional activators (in the presence of HH signaling) and transcriptional repressors (in the absence of HH signaling). This results in a tight control of GLI target gene expression during rapidly changing levels of pathway activity. It has long been presumed that GLI (...) proteins also repress target genes prior to the initial expression of HH in a given tissue. This idea forms the basis for the limb bud pre‐patterning model for regulating digit number. Recent findings indicate that GLI repressor proteins are indeed present prior to HH signaling but contrary to this model, GLI proteins are inert as they do not regulate transcriptional responses or enhancer chromatin modifications at this time. These findings suggest that GLI transcriptional repressor activity is not a default state as assumed, but is itself regulated in an unknown fashion. We discuss these findings and their implications for understanding pre‐patterning, digit regulation, and HH‐driven disease. (shrink)

The Hodgkin–Huxley (HH) model of the action potential is a theoretical pillar of modern neurobiology. In a number of recent publications, Carl Craver ([2006], [2007], [2008]) has argued that the model is explanatorily deficient because it does not reveal enough about underlying molecular mechanisms. I offer an alternative picture of the HH model, according to which it deliberately abstracts from molecular specifics. By doing so, the model explains whole-cell behaviour as the product of a mass of underlying low-level events. The (...) issue goes beyond cellular neurobiology, for the strategy of abstraction exhibited in the HH case is found in a range of biological contexts. I discuss why it has been largely neglected by advocates of the mechanist approach to explanation. 1 Introduction2 A Primer on the HH Model2.1 The basic qualitative picture2.2 The quantitative model3 Interlude: What Did Hodgkin and Huxley Think?4 Craver’s View4.1 Mechanistic explanation4.2 Sketches4.3 Craver's view: The HH model as a mechanism sketch5 An Alternative View of the HH Model5.1 Another look at the equations5.2 The discrete-gating picture5.3 The road paved by Hodgkin and Huxley5.4 Summary and comparison to Craver6 Conclusion: The HH Model and Mechanistic Explanation6.1 Sketches and abstractions6.2 Why has aggregative abstraction been overlooked? (shrink)

Book I of HH would seem to announce the end of Nietzsche's concern with the philosophical pessimism that shapes BT and figures prominently in HL. In BT he endorses the pessimistic thesis that the best thing for a human being is to die soon, while he announces in HH that the even the words "optimism" and "pessimism" are outdated since they play a role in a theological discourse that is gradually dying out. This change is connected with another, namely Nietzsche's (...) growing intolerance of metaphysical speculation of any sort. In place of the wild metaphysics of BT, which postulates Apollinian and Dionysian drives as ultimate constituents of reality and associates the latter with a primal... (shrink)