Insulators play a central role in subdividing the chromosome into a series of discrete topologically independent domains and in ensuring that enhancers and silencers contact their appropriate target genes. In this review we first discuss the general characteristics of insulator elements and their associated protein factors. A growing collection of insulator proteins have been identified including a family of proteins whose expression is developmentally regulated. We next consider several unexpected discoveries that require us to completely rethink how insulators (...) function (and how they can best be assayed). These discoveries also require a reevaluation of how insulators might restrict or orchestrate (by preventing or promoting) interactions between regulatory elements and their target genes. We conclude by connecting these new insights into the mechanisms of insulator action to dynamic changes in the three‐dimensional topology of the chromatin fiber and the generation of specific patterns of gene activity during development and differentiation. (shrink)

The subject of this study, the step forward—which the author felt to be ‘of evolutionary value’—was occasioned by a Delphi discussion. The debate was opened by Varga's (2003, 2006a) contrastive exposition of diagnoses of present history with respect to Hungary's accession to the European Union, offered by some leading Hungarian sociologists (Henrik Kreutz, Kálmán Kulcsár, Iván Szelényi, Iván Vitányi), in which he tried to place the views of these authors in a value sociological system by Charles Morris (1956, 1964) and (...) Geert Hofstede (1991). In Morris’ case, this involved recourse to his combination of two systems: one semiotic, the other axiological; in Hofstede's, to his system of ‘software of the mind’ embracing axiology and organizational psychology. This synthesis was opposed by Kreutz (2006a) who offered a new ordering principle which he advanced as truer to life. The present confrontation between the value sociological synthesis advanced by Kreutz, on the one hand, and the trends hallmarked by the names of Morris and Hofstede, on the other hand, provided the author with an opportunity to find a resolution of the tension between desired and desirable, for which he has gained some side light from Robert K. Merton's (1957) theory of the different degrees of insulation of role–activities from observability by members of the role–set (and which has derived further refinement from Jean–Paul Sartre's conception of ‘glance and shame’). (shrink)

The early discovery of cis‐regulatory elements able to promote transcription of genes over large distances led to the postulate that elements, termed insulators, should also exist that would limit the action of enhancers, LCRs and silencers to defined domains. Such insulators were indeed found during the past fifteen years in a wide range of organisms, from yeast to humans. Recent advances point to an important role of transcription factors in insulator activity and demonstrate that the operational observation of (...) an insulator effect relies on a delicate balance between the “efficiency” of the insulator and that of the element to be counteracted. In addition, genuine insulator elements now appear less common than initially envisaged, and they are only found at loci displaying a high density of coding or regulatory information. Where this is not the case, chromatin domains of opposing properties are thought to confront each other at “fuzzy” boundaries. In this article, we propose models for both fixed and fuzzy boundaries that incorporate probabilistic and dynamic parameters. BioEssays 26:523–532, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

It has been claimed that a key difference between ancient and contemporary skepticism is that, unlike the ancient skeptics, contemporary skeptics consider ordinary beliefs to be insulated from skeptical doubt. In the case of metaethics, this issue is related to the following question: what attitude towards ordinary moral thought and discourse should one adopt if one is a moral skeptic? Whereas moral abolitionists claim that one should do away with ordinary moral thought and discourse altogether, moral fictionalists maintain that, given (...) that morality produces practical benefits, one should continue to make moral utterances and have moral thoughts, while at the same time refraining from asserting such utterances and believing such thoughts. Focusing particularly on Mackie’s skeptical stance, the present essay considers whether the view that first-order moral beliefs are unaffected by moral skepticism is defensible, whether moral fictionalism is compatible with moral insulation, and whether contemporary moral skeptics are in general committed to there being insulation between first- and second-order levels. (shrink)

Insulation is a noticeable phenomenon in the case of most non-Pyrrhonian sceptics about human knowledge. A sceptic is experiencing insulation when his scepticism does not have any effect on his common sense beliefs, and his common sense beliefs do not have any effect on his scepticism. I try to show why this is a puzzling phenomenon, and how it can be explained. It is puzzling because insulation seems to require blindness to one's own epistemic irresponsibility and irrationality, while the sceptic (...) presumably cares a lot about being epistemically responsible and rational. Insulation can be explained by means of a notion of philosophical detachment: to be detached from one's own beliefs about the world is to take an other-personal position towards those beliefs, treating them as if they are another person's beliefs. It is because of this that the sceptic's scepticism is insulated from his scepticism because he cannot be detached from his beliefs about the world when he is engaging in everyday, practical activities. I conclude the paper with a brief discussion of the generality of the problem of insulation. (shrink)

In the early 1800s galvanometers could be constructed with the fine gauges of silk-covered copper or silver wires produced for decorative purposes, but when Faraday was making his classic electrical experiments in 1831 he needed a sturdier gauge of copper wire. Bare copper wire was available in many diameters for mechanical applications, but coils for electromagnetic investigations had to be insulated with string and calico. It was soon realized that the cotton-covered springy iron wire then used to hold out the (...) brims of ladies' bonnets showed how copper wire might be similarly wrapped to provide a flexible insulation. The simple manual machines used by the bonnet-wire makers were readily adapted and improved, and a six-head version was built by William Henley. This craftsman's vision of the growing importance of insulated copper wire was abundantly justified, and he built up a large—but poorly organised—empire in the wire and cable trade. Henley's original multiple-head wrapping machine has been located in the Science Museum, London, and the associated silk-covered copper wire subjected to physical, chemical, and electrical testing. For comparison, the electrical conductivity of the ‘mechanical grade’ copper wire used by Faraday has also been determined. (shrink)

This paper interrogates the idea of a virtue-first approach to the question of what has fundamental epistemic value. It has been suggested that a virtue-first approach is needed to strengthen the view known as veritism, according to which only truth has fundamental epistemic value. I distinguish between an ontological and a methodological virtue-first approach, and suggest that only the latter is an attractive option for a veritist. I then argue that the methodological virtue-first approach is incompatible with the idea that (...) the epistemic domain is insulated, in the sense that being of epistemic value does not entail being of value. But insulationism is arguably an important tool for veritists in meeting various objections to their view, aside from being considered generally attractive by many. Veritists thus face a dilemma that requires them to give up one of two arguably attractive tools in their kit: either the virtue-first motivation of their view, or the insulationist conception of epistemic value. (shrink)

Topologically associating domain (TAD) boundaries are the flanking edges of TADs, also known as insulated neighborhoods, within the 3D structure of genomes. A prominent feature of TAD boundaries in mammalian genomes is the enrichment of clustered CTCF sites often with mixed orientations, which can either block or facilitate enhancer–promoter (E‐P) interactions within or across distinct TADs, respectively. We will discuss recent progress in the understanding of fundamental organizing principles of the clustered CTCF insulator codes at TAD boundaries. Specifically, both inward‐ (...) and outward‐oriented CTCF sites function as topological chromatin insulators by asymmetrically blocking improper TAD‐boundary‐crossing cohesin loop extrusion. In addition, boundary stacking and enhancer clustering facilitate long‐distance E‐P interactions across multiple TADs. Finally, we provide a unified mechanism for RNA‐mediated TAD boundary function via R‐loop formation for both insulation and facilitation. This mechanism of TAD boundary formation and insulation has interesting implications not only on how the 3D genome folds in the Euclidean nuclear space but also on how the specificity of E‐P interactions is developmentally regulated. (shrink)

What are conspiracy theories? And what, if anything, is epistemically wrong with them? I offer an account on which conspiracy theories are a unique way of holding a belief in a conspiracy. Specifically, I take conspiracy theories to be self-insulating beliefs in conspiracies. On this view, conspiracy theorists have their conspiratorial beliefs in a way that is immune to revision by counter-evidence. I argue that conspiracy theories are always irrational. Although conspiracy theories involve an expectation to encounter some seemingly disconfirming (...) evidence (allegedly planted by the conspirators), resistance to all counter- evidence cannot be justified on these grounds. (shrink)

Religion is often singled out for special legal treatment in Western societies - which raises an important question: what, if anything, is special about religious conscience beliefs that warrants such special legal treatment? In this paper, I will offer an answer to this specialness question by investigating the relationship between religious conscientious objections and their insulation from relevant evidence. I will begin my analysis by looking at Brian Leiter’s arguments that religious beliefs are insulated from evidence and not worthy of (...) special legal treatment as a result. I will argue that he fails to show that religious conscience beliefs are both in principle responsive to empirical evidence and in practice typically more insulated from this evidence than secular conscience beliefs. If I am right about this, then Leiter fails to answer the “central puzzle” of his recent book and fails to sufficiently distinguish the religious conscience from the secular conscience. Second, I will look at whether or not it is plausible to understand the religious conscience as insulated from other forms of evidence. Following the research of social-psychologist Jonathan Haidt, I will argue that, typically, both forms of conscience seem to be similarly insulated from moral argumentation. I will also show that, while it seems as though the religious conscience usually draws from a larger set of moral values when compared to the secular conscience, this should make no legal difference overall. To conclude, I will explain that the arguments in this paper can be understood as evidence in support of an egalitarian response to religion’s specialness. (shrink)

Punishment and democracy appear to exacerbate each other’s worst features. The institutions and moral intuitions used to punish those that break the law can hollow out civic participation, distort the electorate, and undermine core democratic values. Likewise, many have argued the decentralized character of democracy is a key, albeit indirect, cause of increasingly punitive public policies that are divorced from any reasonable penological purpose. Given the effects of electoral politics, many have called for the separation, or general insulation, of state (...) punishment from public influence. However, recent empirical work on punitive attitudes and institutional design has begun to chip away at this common sense. This article contextualizes and qualifies the various mechanisms of policy feedback and public opinion formation thought by political theorists to undermine democratic participation in penal institutions and makes a normative case that insulating the public from penal law actively sustains injustice. (shrink)

Gene therapy has emerged from the idea of inserting a wild‐type copy of a gene in order to restore the proper expression and function of a damaged gene. Initial efforts have focused on finding the proper vector and delivery method to introduce a corrected gene to the affected tissue or cell type. Even though these first attempts are clearly promising, seveal problems remain unsolved. A major problem is the influence of chromatin structure on transgene expression. To overcome chromatin‐dependent repressive transgenic (...) states, researchers have begun to use chromatin regulatory elements to drive transgene expression. Insulators or chromatin boundaries are able to protect a transgene against chromatin position effects at their genomic integration sites, and they are able to maintain transgene expression for long periods of time. Therefore, these elements may be very useful tools in gene therapy applications for ensuring high‐level and stable expression of transgenes. BioEssays 26:796–807, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

In this research work, we have explored the physical and topological properties of the crystal structure of metal-insulator transition superlattice. In recent times, two-dimensional substantial have enamored comprehensive considerations owing to their novel ophthalmic and mechanical properties for anticipated employment. Recently, some researchers put their interest in modifying this material into useful forms in human life. Also, Metal-Insulator Transition Superlattice is useful in form of a thin film to utilize as two-dimensional transition metal dichalcogenides. Moreover, we have defined the computed-based (...) bond properties such as the degree constructed topological indices and their heat of formation for single crystal and monolayered structure of Ge-Sb-Te. Also, this structure is one of the most interesting composites in modern resources of science. (shrink)

Ethical controversy over transplantation of human fetal tissue has arisen because the source of tissue is induced abortions. Opposition to such transplants has been based on various arguments, including the following: rightful informed consent cannot be obtained for use of fetal tissue from induced abortions, and fetal tissue transplantation might result in an increase in the number of abortions. These arguments were not accepted by the National Institutes of Health (NIH) Human Fetal Tissue Transplantation Research Panel. The majority opinion of (...) the panel stated that abortion and fetal tissue use are entirely separate issues, and that tissue use is ethically acceptable because it can be morally insulated from the issue of abortion. In support of this view, panel members and others have replied to the arguments put forward by opponents of fetal tissue use. However, replies to the two arguments mentioned above have been unsatisfactory, and the shortcomings of those replies are identified herein. Examination of the arguments pro and con suggests that fetal tissue use cannot be completely insulated from the issue of abortion. Thus, in seeking an ethical justification for fetal tissue transplantation we must consider reasons other than those put forward by the NIH panel. In this paper it is argued that whatever wrong is involved in using fetal tissue from induced abortions must be balanced against the benefits for patients, and it is on this basis that fetal tissue transplantation can be ethically justified. (shrink)

Is it rational to believe that the mind is identical to the brain? Identity theorists say it is (or looks like it will be, once all the neuroscientific evidence is in), and they base this claim on a general epistemic route to belief in identity. I re-develop this general route and defend it against some objections. Then I discuss how rational belief in mind–brain identity, obtained via this route, can be threatened by an appropriately adjusted version of the anti-physicalist knowledge (...) argument. Responses to this threat usually appeal either to different modes of presentation or to phenomenal concepts. But neither type of response is satisfactory. I provide a novel response, which appeals to an innocuous epistemic peculiarity of phenomenal states, namely their, as I shall call it, evidential insulation. (shrink)

The main bioclimatic passive strategies include optimization of the use of natural light, reducing the need for artificial light, maximizing the solar gain using thermal traps and promotion of natural ventilation in order to avoid the need for air conditioning for cooling. The usage of cool air passing through the underground tunnels located in the selected neighborhood in Tirana in order to enhance the cooling process is of huge importance. On the other hand, the building must benefit from the passive (...) solar systems and thermal energy conservation strategies implementing thermal insulation materials. These strategies improve both the indoor comfort and economic aspect. The aim is to be aware of the community for the big benefits of such strategies, increasing the number of passive bioclimatic implementations not only in Albania but also in the region. Through the use of such systems the building can obtain indoor thermal comfort without a traditional cooling system. The passive systems discourage the use of mechanical systems for lighting, cooling, and heating, supporting the natural phenomena such as power of the sun, underground constant temperature, wind direction, and other climate parameters. The selection of the proper thermal insulation materials is complex and sometimes determinant in order to reduce heat gain. The thermal accumulation capacity depends on material width, material type, density, and porosity of the material. The top insulating materials are mostly used in the Tirana. Albania is the expanded polystyrene (EPS). The energy needed for its production is relatively low compared to the other insulating materials. Passive design encourages the application of such kind of materials, reducing the ecological footprint of the buildings. Water recycling is another aspect that bioclimatic design takes into consideration, promoting it. The use of specific materials in order to recycle the rain water through drainage is an important task. The building is faced with significant thermal losses due to the windows. The sizing of the glass area, the orientation, as well as the choice of glass determine the penetration of solar radiation in the building. The selection of the correct type of window is also a complex task. The designer should consider the climate type, the area of the openings, the typology of the window, and the characteristics of the window materials and its thermal performance before implementing it. The usage of the high thermal capacity materials (stone, water) is getting noticed nowadays in bioclimatic and passive building designs. These materials are efficient when having large surfaces and face a strong solar radiation. PCM (phase change materials) are innovative materials that undergo a physical transformation stabilizing the temperature fluctuations in the indoor area of the building archiving and improving thermal comfort parameters inside the building. The typology of such materials and their field of implementation is a very large one. Such materials have resulted to be an added value when implemented and are part of passive systems such as Trombe wall, enhancing its performance. The piezo-electric materials are another group of innovative materials used to gain energy. Their role in energy gaining nowadays is very small but the future belongs to them. The use of such materials is promoted by bioclimatic design benefiting by their mechanical properties, producing electricity. The Empathic house is one of the examples of the future generations. The implementation of some other materials such as ETFE in the building envelope in contrast to glass allows the long-wave penetration inside the building increasing the solar gain capacity. The visibility of such materials is still under examination. (shrink)

This paper presents information about the moisture content and temperature level of brick walls in Tirana, Albania. The buildings whose walls have been studied were built in two different eras, throughout the twentieth century, and in more recent times. Given that during the second half of the twentieth century, Albania has been isolated from most of Europe and the West, and consequently the new architectural ideologies of the time, have not had the proper implementation there, the paper focuses on the (...) characteristic types of bricks used in Albania, the functions for which they are used, and their effectiveness in achieving comfort (thermal, moisture content control) during the two time periods mentioned above. Depending on the functions bricks perform in the walls studied in this paper, the walls are separated into two main groups: Walls in which bricks have structural role (red silicate brick walls, white silicate brick walls) and walls in which bricks do not have structural role (concrete block walls, holed brick walls). For all the types of bricks mentioned above, indoor moisture content and temperature measurements have been performed in all four cardinal directions. For the walls in which the bricks have a structural function, moisture measurements have been performed in all the facades of the buildings, because moisture in the bricks of these types of buildings, being a very important factor, directly affects the structural performance of the elements. The aim of the paper is to show the differences in moisture and temperature levels of the walls of these buildings, depending on the engineering and architectural techniques used during the building process, the use of insulation, and the masonry composition. (shrink)

Extruded polystyrene (XPS) otherwise known as a thermoplastic polymer has a closed cell structure and is often stronger, with a higher mechanical performance. XPS is a pressed material and is sold in different thicknesses ranging from 2 cm to 10 cm, thus having a weight that varies from 28 to 45 kg/m3 due to the force and pressure exerted on it. In general, XPS material has very low thermal conductivity and is resistant to bending. This material obtains typical values of (...) thermal conductivity between 0.025 and 0.040 W/m∙K., which means that it is ideal for surfaces that have to withstand weight, continuous traffic, etc. It is also resistant to moisture absorption and has a homogeneous density. Other characteristics of the material are good acoustic properties, easy assembly, and high durability over time. It should always be kept in mind that the surface where the thermal insulation will be applied must be leveled, cleaned, and dried. Primer is applied, before placing the thermal insulation on the surface. Then, XPS boards are placed on the surface, adhering to the corresponding mortar. This paper will deal with different cases of application of XPS tiles in the city of Tirana. A closer look at the resistance of this material from the day of application until today will be analyzed. The results during the observations showed high thermal stability of the material and no mold surface. EPS Expanded Polystyrene, otherwise known by the Dow Chemical trademark name STYROFOAM, is a lightweight product made from expanded plastic beads. It was first discovered by Eduard Simon in 1839 in Germany. EPS in its composition has 95% air and only about 5% plastic. This material is used because of its excellent properties, including good thermal insulation, good protective properties, and extremely lightweight. EPS is inert in nature and therefore does not result in any chemical reaction. EPS is durable, strong, and lightweight and can be used as an insulated panel system for facades, walls, roofs, and floors, as floating material in marine construction, and as a lightweight filler in road and railway construction. Different examples from the city of Tirana, of buildings where XPS and EPS materials are applied, are going to be analyzed, drawing conclusions. (shrink)

This article presents information about facades, their thermal insulating role in buildings in Albania. The façade in construction is one of the necessary factors to ensure a longer life of the buildings and indoor thermal comfort. Façade systems are composed of different materials, which provide a protective effect during the life of the building. The article will focus on the characteristic materials used in Albania for the construction of facades and the main materials used from the year 2000 up to (...) today. The article will be informative, statistical, and comparative in order to draw conclusions. Nowadays building facades are again becoming one of the main subjects of discussion, undoubtedly due to the increasing importance of the building envelope in relation to energy consumption. In the 90s, minimal attention was paid to the efficiency and quality of facades; everything was done strictly in relation to residency requirements. But, during this last decade, Albania experienced a construction boom, with a series of good new buildings, which are accompanied by progress in the architectural style and in the techniques of building materials usage. However, the advantages of façade systems in construction are not only to make the building long-lasting. The function of facades always undergoes changes and advances over time, in terms of their impact on the temperature fluctuations inside the building or energy storage. (shrink)

Recent literature on skepticism has raised a nearly univocal voice in condemning skeptical argumentation on the grounds that such argumentation necessarily involves our adopting some nonordinary or unnatural perspective. Were this really so, then skeptical conclusions would not speak to us in the way in which skeptics think they do: We would be "insulated" from any such conclusions. I argue that skeptical argumentation need not rely on any nonordinary or unnatural standards. Rather, the skeptic's procedure is to offer a critique (...) from within. Having given my argument for this claim (which I call the 'continuity argument'), I consider and respond to two important objections. I conclude that the skeptic has a powerful meta-argument to be deployed in defending the legitimacy of his skeptical conclusions against the slings and arrows of (those I call) the half-true theorists. (shrink)

This paper determines the acoustic properties of external wall building materials composition. Noise pollution is one of the main pollutants nowadays but it is not considered of great importance in the construction field, despite some studies showing that greater acoustic pollution is produced by buildings under construction. The study consists of analysing two different types of buildings equipped with a different type of external masonry composition in terms of building materials. The buildings are located at “21 Dhjetori” street, Tirana, Albania. (...) Furthermore, the case study area is treated as an area that consistently harvests noise. The impact of noise pollution on the existing building materials is going to be analyzed. Those milestones will provide information regarding the noise levels, a comparison of the actual level of noise production (outdoor and indoor areas), sound transmission, and sound diminution, as well as the implementation of acoustic materials in order to improve the quality of life of the inhabitants. The selected area has the highest norms of acoustic pollution in the city according to the studies implemented by Determination of acoustic properties of building materials is an important task gaining higher importance due to the demand for suitable construction materials, located in places with high levels of noise and places with heavy traffic, such as in urban areas. The aim of this paper is to display a comparative study of the actual noise levels generated by this area. It indicates the acoustic properties of the current building materials followed by a more suitable soundproof insulation. (shrink)

We argue that neuroeconomics should be a mechanistic science. We defend this view as preferable both to a revolutionary perspective, according to which classical economics is eliminated in favour of neuroeconomics, and to a classical economic perspective, according to which economics is insulated from facts about psychology and neuroscience. We argue that, like other mechanistic sciences, neuroeconomics will earn its keep to the extent that it either reconfigures how economists think about decision-making or how neuroscientists think about brain mechanisms underlying (...) behaviour. We discuss some ways that the search for mechanisms can bring about such top-down and bottom-up revision, and we consider some examples from the recent neuroeconomics literature of how varieties of progress of this sort might be achieved. (shrink)