Rationale In Belgium, several policies regulating reimbursement of acid suppressant drugs and evidence-based recommendations for clinical practice were issued in a short period of time, creating a unique opportunity to observe their effect on prescribing. Aims and objectives To describe the evolution of prescriptions for acid suppressants and explore the interaction of policies and practice recommendations with prescribing patterns. Method Monthly claims-based data for proton pump inhibitors (PPIs) and H-2-antihistamines by general practitioners, internists and "astroenterologists were obtained (...) from the Belgian national health insurance database (1997-2005). The evolution of reimbursed defined daily doses and expenses after introduction of reimbursement regulations and dissemination of practice recommendations was explored. Results Recommendations had no impact on prescribing. All changes can be related to concomitant policies. Lifting reimbursement restrictions for cheaper products did not control growth or save costs in the Iona term. Only restricting reimbursement of all PPIs managed to curb the growth. We observed an unintended increase of non-omeprazole PPIs by gastroenterologists. Conclusions Reimbursement policies influence prescribing, but their effect can be unintended. A dialogue between policymakers and guideline developers, and evidence-based policies that are linked to clinical guidelines, could be an effective way to pursue both cost-containment and quality of care. (shrink)

Ductin is the highest conserved membrane protein yet found in eukaryotes. It is multifunctional, being the subunit c or proteolipid component of the vacuolar H+‐ATPase and at the same time the protein component of a form of gap junction in metazoan animals. Analysis of its structure shows it to be a tandem repeat of two 8‐kDa domains derived from the subunit c of the F0 proton pore from the F1F0 ATPase. Each domain contains two transmembrane α‐helices, which together may (...) form a four‐helix bundle. In both the V‐ATPase and gap junction channel, ductin is probably arranged as a hexamer of subunits forming a central channel of gap junction‐like proportions. The two functions appear to be seggregated by ductin having two orientations in the bilayer. Ductin is also the major component of the mediatophore, a protein complex which may aid in the release of neurotransmitters across the pre‐synaptic membrane. It is also a target for a class of poorly understood viral polypeptides. These polypeptides are small and highly hydrophobic and some have oncogenic activity. Ductin thus appears to be at the crossroads of a number of biological processes. (shrink)

Rhodopsins are one of the most studied photoreceptor protein families, and ion‐translocating rhodopsins, both pumps and channels, have recently attracted broad attention because of the development of optogenetics. Recently, a new functional class of ion‐pumping rhodopsins, an outward Na+ pump, was discovered, and following structural and functional studies enable us to compare three functionally different ion‐pumping rhodopsins: outward proton pump, inward Cl− pump, and outward Na+ pump. Here, we review the current knowledge on structure‐function relationships (...) in these three light‐driven pumps, mainly focusing on Na+ pumps. A structural and functional comparison reveals both unique and conserved features of these ion pumps, and enhances our understanding about how the structurally similar microbial rhodopsins acquired such diverse functions. We also discuss some unresolved questions and future perspectives in research of ion‐pumping rhodopsins, including optogenetics application and engineering of novel rhodopsins. (shrink)

Vacuolar ATPases (V‐ATPases, V1Vo‐ATPases) are rotary motor proton pumps that acidify intracellular compartments, and, when localized to the plasma membrane, the extracellular space. V‐ATPase is regulated by a unique process referred to as reversible disassembly, wherein V1‐ATPase disengages from Vo proton channel in response to diverse environmental signals. Whereas the disassembly step of this process is ATP dependent, the (re)assembly step is not, but requires the action of a heterotrimeric chaperone referred to as the RAVE complex. Recently, an (...) alternative pathway of holoenzyme disassembly was discovered that involves binding of Oxidation Resistance 1 (Oxr1p), a poorly characterized protein implicated in oxidative stress response. Unlike conventional reversible disassembly, which depends on enzyme activity, Oxr1p induced dissociation can occur in absence of ATP. Yeast Oxr1p belongs to the family of TLDc domain containing proteins that are conserved from yeast to mammals, and have been implicated in V‐ATPase function in a variety of tissues. This brief perspective summarizes what we know about the molecular mechanisms governing both reversible (ATP dependent) and Oxr1p driven (ATP independent) V‐ATPase dissociation into autoinhibited V1 and Vo subcomplexes. (shrink)

This article summarizes the study of anion exchange mechanisms in bacteria. Along with defining at least two different families of anion exchange, an examination of such carrier‐mediated antiport reactions has led to techniques that considerably broaden the scope of biochemical methods for examining membrane proteins. Such advances have been exploited to show that anion exchange itself forms the mechanistic base of an entirely new kind of proton pump, one which may shed light on a variety of bacterial events, (...) including methanogenesis. Perhaps most important, the study of exchange provided the final link in a chain of evidence pointing to a structural [rhythm] that seems to characterize membrane carriers. These three issues ‐ a biochemical tool, a new proton pump, and a common structural rhythm ‐ are briefly examined in the context of their origins in the analysis of bacterial anion exchange. (shrink)

Protons are the most common coupling ions in bacterial energy conversions. However, while many organisms, such as the alkaliphilic Bacilli, employ H+‐bioenergetics for electron transport phosphorylation, they use Na+ as the coupling ion for transport and flagellar movement. The Na+ gradient required for these bioenergetic functions is established by the secondary Na+/H+ antiporter. In contrast, Vibrio alginolyticus and methanogenic bacteria have primary pumps for both H+ and Na+. They use the proton gradient for ATP synthesis while other, less energy‐consuming (...) membrane reactions are powered by the Na+ gradient. In a third mode, some anaerobic bacteria possess decarboxylases acting as primary Na+ pumps. For instance, in Klebsiella pneumoniae, the Na+ gradient established by oxaloacetate decarboxylase is used for the uptake of the growth substrate citrate, and Propionigenium modestum consumes the energy of the Na+ gradient formed by methylmalonyl‐CoA decarboxylase directly for ATP synthesis. (shrink)

BackgroundWhile genomic data sharing can facilitate important health research and discovery benefits, these must be balanced against potential privacy risks and harms to individuals. Understanding public attitudes and perspectives on data sharing is important given these potential risks and to inform genomic research and policy that aligns with public preferences and needs.MethodsA cross sectional online survey measured attitudes towards genomic data sharing among members of the general public in an Eastern Canadian province.ResultsResults showed a moderate comfort level with sharing genomic (...) data, usually into restricted scientific databases with controlled access. Much lower comfort levels were observed for sharing data into open or publicly accessible databases. While respondents largely approved of sharing genomic data for health research permitted by a research ethics board, many general public members were concerned with who would have access to their data, with higher rates of approval for access from clinical or academic actors, but much more limited approval of access from commercial entities or governments. Prior knowledge about sequencing and about research ethics boards were both related to data sharing attitudes.ConclusionsWith evolving regulations and guidelines for genomics research and data sharing, it is important to consider the perspectives of participants most impacted by these changes. Participant information materials and informed consent documents must be explicit about the safeguards in place to protect genomic data and the policies governing the sharing of data. Increased public awareness of the role of research ethics boards and of the need for genomic data sharing more broadly is also needed. (shrink)

Suppose that you prefer A to B, B to C, and C to A. Your preferences violate Expected Utility Theory by being cyclic. Money-pump arguments offer a way to show that such violations are irrational. Suppose that you start with A. Then you should be willing to trade A for C and then C for B. But then, once you have B, you are offered a trade back to A for a small cost. Since you prefer A to B, (...) you pay the small sum to trade from B to A. But now you have been turned into a money pump. You are back to the alternative you started with but with less money. This Element shows how each of the axioms of Expected Utility Theory can be defended by money-pump arguments of this kind. The Element also defends money-pump arguments from the standard objections to this kind of approach. This title is also available as Open Access on Cambridge Core. (shrink)

One of the world’s leading philosophers offers aspiring thinkers his personal trove of mind-stretching thought experiments. Over a storied career, Daniel C. Dennett has engaged questions about science and the workings of the mind. His answers have combined rigorous argument with strong empirical grounding. And a lot of fun. Intuition Pumps and Other Tools for Thinking offers seventy-seven of Dennett’s most successful "imagination-extenders and focus-holders" meant to guide you through some of life’s most treacherous subject matter: evolution, meaning, mind, and (...) free will. With patience and wit, Dennett deftly deploys his thinking tools to gain traction on these thorny issues while offering readers insight into how and why each tool was built. Alongside well-known favorites like Occam’s Razor and reductio ad absurdum lie thrilling descriptions of Dennett’s own creations: Trapped in the Robot Control Room, Beware of the Prime Mammal, and The Wandering Two-Bitser. Ranging across disciplines as diverse as psychology, biology, computer science, and physics, Dennett’s tools embrace in equal measure light-heartedness and accessibility as they welcome uninitiated and seasoned readers alike. As always, his goal remains to teach you how to "think reliably and even gracefully about really hard questions." A sweeping work of intellectual seriousness that’s also studded with impish delights, Intuition Pumps offers intrepid thinkers—in all walks of life—delicious opportunities to explore their pet ideas with new powers. (shrink)

The Money Pump argument is designed to demonstrate the irrational flaw of having cyclic preferences, by showing how the irrational agent is vulnerable to exploitation. The argument faces some longstanding objections, which point out how one may avoid the threat of exploitation without resolving the associated irrationality. Recently a new, synchronic version of Money Pump has been put forward which promises to undercut those standard objections. However, I argue that the synchronic Money Pump cannot deliver on its (...) promise: parallel objections can be reconstructed for this version, too, demonstrating that it ultimately does not improve on the original. (shrink)

The idea that rational agents should have acyclic preferences and should obey conditionalization has been defended on the grounds that otherwise an agent is threatened with becoming a “money pump.” This essay argues that such arguments fail to prove their claims.

I begin with an explication of “thought experiment”. I then clarify the role that intuitions play in thought experiments by addressing two important issues: the informativeness of thought experiments and the legitimacy of the method of thought experiments in philosophy and the natural sciences. I defend a naturalistic account of intuitions that provides a plausible explanation of the informativeness of thought experiments, which, in turn, allows thought experiments to be reconstructed as arguments. I also specify criteria for distinguishing bad “intuition (...) pumps” from legitimate thought experiments. These criteria help us to avoid being seduced by the dangerous suggestive power of misleading intuitions. (shrink)

I begin with an explication of "thought experiment". I then clarify the role that intuitions play in thought experiments by addressing two important issues: (1) the informativeness of thought experiments and (2) the legitimacy of the method of thought experiments in philosophy and the natural sciences. I defend a naturalistic account of intuitions that provides a plausible explanation of the informativeness of thought experiments, which, in turn, allows thought experiments to be reconstructed as arguments. I also specify criteria for distinguishing (...) bad "intuition pumps" from legitimate thought experiments. These criteria help us to avoid being seduced by the dangerous suggestive power of misleading intuitions. (shrink)

The idea that rational agents should have acyclic preferences and should obey conditionalization has been defended on the grounds that otherwise an agent is threatened with becoming a “money pump.” This essay argues that such arguments fail to prove their claims.

So-called money pump arguments aim to show that intransitive preferences are irrational because they will lead someone to accept a series of deals that leaves his/her financially worse off and better off in no respect. A common response to these arguments is the foresight response, which counters that the agent in question may see the exploitation coming, and refuse to trade at all. To obviate this response, I offer a “deluxe money pump argument” that applies dominance reasoning to (...) a modified money pump case. (shrink)

I describe in section 1 how cyclical preferences can arise. In section 2, I relate preference to judgments of choiceworthiness and distinguish between two kinds of preference cycles, vicious and benign. In section 3, I run through the standard money pump in order to show, in section 4, how this pump can be stopped by foresight, using backward induction. A new money pump that *cannot* be stopped by foresight is presented in section 5. This pump works (...) even for agents with benign cyclical preferences. What makes it work is persistency on the part of the would-be exploiter. In section 6, I compare this pump to a diachronic Dutch book that can be set up against someone whose probability assignments violate Reflection. Even in this case, the book only works if the bookie is assumed to be persistent. I use this comparison between preference cyclicity and violations of Reflection in order to question whether exploitability must be seen as a proof of irrationality. Finally, in section 7, I consider resolute choice as an alternative to the backward-induction procedure. While a resolute chooser cannot be exploited, I argue that resoluteness is not required by rationality. The argument is based on a suggestion that rationality, when it comes to actions, is a local rather than a global requirement. (shrink)

After maintaining in that certain cyclical preferences can be reasonable, the following questions were tabled: “in what circumstances and under what assumptions … these … preferences of George's would turn him into a ”money pump,” and in what circumstances and under what assumptions they would not do that.” Two pumps afford answers. George, who is sufficiently reasonable and well-informed to use backward induction, has, for this reason, nothing to fear from the first pump, but the second, of a (...) nonstandard design by Wlodek Rabinowicz, ruins him just because he is subject to the constraints of backward induction. Could he be helped by extending his options from actions in a single round, to courses of actions starting in that round? Possibly not. He would be safe if he were capable of resolute choices of couses of action. Even so, he is in trouble through no fault of his, if, as I think, not having that capacity, though a misfortune, is not a fault. (shrink)

I describe in section 1 how cyclical preferences can arise. In section 2, I relate preference to judgments of choiceworthiness and distinguish between two kinds of preference cycles, vicious and benign. In section 3, I run through the standard money pump in order to show, in section 4, how this pump can be stopped by foresight, using backward induction. A new money pump that *cannot* be stopped by foresight is presented in section 5. This pump works (...) even for agents with benign cyclical preferences. What makes it work is persistency on the part of the would-be exploiter. In section 6, I compare this pump to a diachronic Dutch book that can be set up against someone whose probability assignments violate Reflection. Even in this case, the book only works if the bookie is assumed to be persistent. I use this comparison between preference cyclicity and violations of Reflection in order to question whether exploitability must be seen as a proof of irrationality. Finally, in section 7, I consider resolute choice as an alternative to the backward-induction procedure. While a resolute chooser cannot be exploited, I argue that resoluteness is not required by rationality. The argument is based on a suggestion that rationality, when it comes to actions, is a local rather than a global requirement. (shrink)

One might think that money pumps directed at agents with cyclic preferences can be avoided by foresight. This view was challenged two decades ago by the discovery of a money pump with foresight, which works against agents who use backward induction. But backward induction implausibly assumes that the agent would act rationally and retain her trust in her future rationality even at choice nodes that could only be reached if she were to act irrationally. This worry does not apply (...) to BI-terminating decision problems, where at each choice node backward induction prescribes a move that terminates further action. For BI-terminating decision problems, it is enough to assume that rationality and trust in rationality are retained at choice nodes reachable by rational moves. The old money pump with foresight was not BI-terminating. In this paper, we present a new money pump with foresight, one that is both BI-terminating and considerably simpler. (shrink)

The title is not a metaphor, though past tense might be better as this chapter is about how each of the many hundred abrupt coolings of the last several million years could have served as a pump stroke, each elevating intelligence a small increment - even though what natural selection was operating on was not intelligence per se.

Every year our sun should be losing about 10 20 protons (about a milligram's worth) in this way. This is not much of a loss, but it is irreversible, and it adds up. In 10..

The award of the 2003 Barwise Prize to Daniel Dennett by the American Philosophical Association signifies Dennett’s importance in the developing area of philosophical inquiry into computing and information. One source of Dennett’s intellectual stature is his command of scientific and engineering ideas, which he effectively applies to philosophical debates over machine intelligence, consciousness, and intentionality. Dennett regards the computer as both a model and a tool that will transform the ways that philosophy is pursued in the 21st century. In (...) order to understand Dennett’s conception of how philosophy changes and fares, if his mechanistic and reductionist conception of the life of the mind succeeds, we turn to an examination of a central idea in Dennett’s thought: the intuition pump. (shrink)

It is proposed in this paper that enzymes, by virtue of a number of correctly positioned sites of interaction with substrates, can force the compression of hydrogen bonds, increasing the probability of proton transfer by quantum mechanical tunneling. By such a catalytic mechanism a rate enhancement of many orders of magnitude may be obtained with a very low energy input requirement. The mechanism would, however, require a highly structured catalyst.Pertinent aspects of hydrogen bond theory and of tunneling theory are (...) briefly reviewed. (shrink)

A money-pump is a thought experiment involving a person whose preferences form a circle. Repeatedly, she pays some money to go from one alternative to another that she likes better. When she has paid her way around the full circle she is back at the starting-point, but with less money. Money-pumps have been used to show that certain preference patterns are irrational since they make a person exploitable. Formal tools can be used to analyze money-pumps in a precise manner, (...) distinguish between different types of money-pumps, and investigate decision strategies to avoid their pernicious effects. Although money-pumps are rather contrived constructions, these investigations have practical relevance since there seem to be decision situations in the real world with the same structure. (shrink)

The money-pump argument figures as the staple argument in support of the view that cyclic preferences are irrational. According to a prominent way of understanding the argument, it is grounded in the assumption that it is irrational to make choices that lead one to a dispreferred alternative. My aim in this paper is to motivate diffidence with respect to understanding the money-pump argument in this way by suggesting that if it is so understood, the argument emerges as question-begging (...) and as a complicated distraction in the debate concerning cyclic preferences, and that there is a way of understanding the argument that casts it as grounded in a less controversial starting point. (shrink)

In an alleged counter-example to the completeness of rational preferences, a career as a clarinettist is compared with a career in law. It seems reasonable to neither want to judge that the law career is at least as preferred as the clarinet career nor want to judge that the clarinet career is at least as preferred as the law career. The two standard interpretations of examples of this kind are, first, that the examples show that preferences are rationally permitted to (...) be incomplete and, second, that the examples show that preferences are rationally permitted to be indeterminate. In this paper, I shall argue that the difference between these interpretations is crucial for the money-pump argument for transitivity, which is the standard argument that rational preferences are transitive. I shall argue that the money-pump argument for transitivity fails if preferences are rationally permitted to be incomplete but that it works if preferences are rationally permitted to be indeterminate and rationally required to be complete. (shrink)

The initial relationships between organisms leading to endosymbiosis and the first eukaryote are currently a topic of hot debate. Here, I present a theory that offers a gradual scenario in which the origins of phagocytosis and mitochondria are intertwined in such a way that the evolution of one would not be possible without the other. In this scenario, the premitochondrial bacterial symbiont became initially associated with a protophagocytic host on the basis of cooperation to kill prey with symbiont‐produced toxins and (...) reactive oxygen species (ROS). Subsequently, the cooperation was focused on the digestion stage, through the acidification of the protophagocytic cavities via exportation of protons produced by the aerobic respiration of the symbiont. The host gained an improved phagocytic capacity and the symbiont received organic compounds from prey. As the host gradually lost its membrane energetics to develop lysosomal digestion, respiration was centralized in the premitochondrial symbiont for energy production for the consortium. (shrink)

Recent evidence indicates that the presence of serine proteinase inhibitors in plant leaves can reduce predation by insects. Plants can now be transformed with proteinase inhibitor genes with strong promoters to express the inhibitor proteins in relatively high levels at specific times. Inhibitors having variable specificities against digestive proteinases of insects and pathogens can now be assessed for their possible role(s) in natural plant defense and for their potential usefulness in protecting crop plants against herbivores.

Chemiosmotic coupling − the harnessing of electrochemical ion gradients across membranes to drive metabolism − is as universally conserved as the genetic code. As argued previously in these pages, such deep conservation suggests that ion gradients arose early in evolution, and might have played a role in the origin of life. Alkaline hydrothermal vents harbour pH gradients of similar polarity and magnitude to those employed by modern cells, one of many properties that make them attractive models for life's origin. Their (...) congruence with the physiology of anaerobic autotrophs that use the acetyl CoA pathway to fix CO2 gives the alkaline vent model broad appeal to biologists. Recently, however, a paper by Baz Jackson criticized the hypothesis, concluding that natural pH gradients were unlikely to have played any role in the origin of life. Unfortunately, Jackson mainly criticized his own interpretations of the theory, not what the literature says. This counterpoint is intended to set the record straight. (shrink)

In “The Irrelevance of the Diachronic Money-Pump Argument for Acyclicity,” The Journal of Philosophy CX, 8 (August 2013), 460-464, Johan E. Gustafsson contends that if Davidson, McKinsey and Suppes’ diachronic money-pump argument in their "Outlines of a Formal Theory of Value, I," Philosophy of Science 22 (1955), 140-160 is valid, so is the synchronic argument Gustafsson himself offers. He concludes that the latter renders irrelevant diachronic choice considerations in general, and the two best-known diachronic solutions to the money (...) pump problem in particular. I argue here that this reasoning is incorrect, and that Gustafsson’s synchronic argument is faulty on independent grounds. Specifically, it is based on a false analogy between the derivation of a synchronic ordinal ranking from a transitive series of pairwise comparisons, and the putative derivation of such a ranking from an intransitive series. The latter is not possible under the assumption of revealed preference theory, and is highly improbable even if that assumption is rejected. Moreover, Gustafsson’s argument raises issues of fidelity to the historical texts that must be addressed. I conclude that the money pump, and cyclical choice more generally, are necessarily diachronic; and therefore that the two best-known diachronic solutions to the money pump problem remain relevant. (shrink)

In a new introduction, the authors describe how science and its social context were understood when this book was first published, and how the study of the history of science has changed since then.

Corballis's explanation for right-handedness in humans relies heavily on the gestural protolanguage hypothesis, which he argues for by a series of “intuition pumps.” Scrutinizing the mirror system hypothesis and modern gesture as components of the argument, we find that they do not provide the desired evidence of a gestural precursor to speech.

Histone deacetylase inhibitors (HDACi) are in clinical trials against a variety of cancers. Despite early successes, results against the more common solid tumors have been mixed. How is it that so many cancers, and most normal cells, tolerate the disruption caused by HDACi‐induced protein hyperacetylation? And why are a few cancers so sensitive? Here we discuss recent results showing that human cells mount a coordinated transcriptional response to HDACi that mitigates their toxic effects. We present a hypothetical signaling system (...) that could trigger and mediate this response. To account for the existence of such a response, we note that HDACi of various chemical types are made by a variety of organisms to kill or suppress competitors. We suggest that the resistance response in human cells is a necessary evolutionary consequence of exposure to environmental HDACi. We speculate that cancers sensitive to HDACi are those in which the resistance response has been compromised by mutation. Identifying such mutations will allow targeting of HDACi therapy to potentially susceptible cancers. (shrink)

The paper's focus is on pragmatic arguments for various ‘rationality constraints’ on a decision maker’s state of mind: on his beliefs or preferences. An argument of this kind purports to show that a violator of a given constraint can be exposed to a decision problem in which he will act to his guaranteed disadvantage. Dramatically put, he can be exploited by a clever bookie who doesn’t know more than the agent himself. Examples of pragmatic arguments of this kind are synchronic (...) Dutch Books, for the standard probability axioms, diachronic Dutch Books, for the more controversial principles of reflection and conditionalization, and Money Pumps, for the transitivity requirement on preferences. The proposed exploitation set-ups share a common feature. If the violator of a given constraint is logically and mathematically competent, he can be exploited only if he is disunified in his decision-making. Exploitation is possible only if the agent makes decisions on various issues he confronts one by one, rather than on all of them together. Unity in decision making may be quite costly and is often inconvenient, especially when it concerns opportunity packages that are spread over time. Therefore, pragmatic arguments should be seen as delivering conditional conclusions: “To afford being disunified as a decision maker, you’d better satisfy these constraints.” Arguments of this kind fail to establish the inherent rationality of the constraints under consideration. Levi’s view of the status of pragmatic arguments (cf. Levi 2002) is diametrally opposed. According to him, only synchronic pragmatic arguments are valid (indeed, categorically valid). The diachronic ones, he argues, lack any validity at all. This line of reasoning is questioned in the paper. (shrink)

If the universe is teeming with intelligent alien life, as many SF stories would have us believe, why has nobody come to visit us or even beamed us a radio message? David Brin's excellent science-fact article "Just How Dangerous is the Galaxy?" ANALOG, July 1985) was a very comprehensive survey of possible explanations for The Great Silence, "the strange and apparently longstanding absence of intelligent extraterrestrial life". By any standard this article is a contender for best-of-the-year science fact article in (...) any SF magazine. If you haven't read it yet you should dig out your back issues and do so. (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 (...) class='Hi'>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)

A novel photon-based proton model is developed. A proton’s ground state is assumed to be coherent to the degree that all of its mass-energy precipitates into a single uncharged spherical structure. A quantum vortex, initiated by the strong force, but sustained in the proton’s ground state by the circular Unruh effect and a spherical Rindler horizon, is proposed to confine the proton’s mass-energy in its ground state. A direct connection between the circular Unruh effect, the zitterbewegung (...) effect, spin, and general relativity is proposed. Such a structure acts as an uncharged zitterbewegung fermion, and may explain neutrino mass. A ground-state proton’s central zitterbewegung fermion is assumed to be surrounded by a halo of charge shells of both signs. Virtual photon standing waves are assumed to synchronize the inner shell with the central zitterbewegung fermion. The charge shells are proposed to be associated with isospin and proton g-factor. There are only two model inputs—proton mass and quantized electronic charge—and just one adjustable parameter. The adjustable parameter, reduced only by about 0.4% from an initial estimate, provides the proton’s experimentally determined magnetic moment to arbitrary precision. The resulting modeled proton charge radius agrees very well with the 2018 CODATA value. Magnetic moment and charge radius are calculated algebraically in a manner easily understood by undergraduate physics students. This proposed ground-state proton model could be considered a low-energy approximation to a full quantum chromodynamical proton model. (shrink)

This paper investigates the drivers and inhibitors of Internet privacy concern. Applying the Multidimensional Development Theory to the online environment, we identify the important factors under four dimensions—i.e., environmental, individual, information management, and interaction management. We tested our model using data from an online survey of 2417 individuals in Hong Kong. The results show that the factors under all four dimensions are significant in the formation of Internet privacy concern. Specifically, familiarity with government legislation, Internet knowledge, benefit of information (...) disclosure, privacy protection, and social presence reduce Internet privacy concern, while individuals’ previous privacy invasion experience, risk avoidance personality, and sensitivity of information requested by websites increase Internet privacy concern. We conducted an analysis of unobserved heterogeneity to confirm the significance of these factors. A follow-up moderation analysis shows that the individual factors moderate the effects of the information management factor and the interaction management factors. The findings provide an integrated understanding of the formation of Internet privacy concern. (shrink)