This article theoretically proposes and empirically verifies an understudied issue in the business ethics and corporate social responsibility literature—how moral degradation in a society influences the relationship between BE or CSR and firm performance. Building on strategic choice theory, we propose that both BE and CSR become more important in enhancing business success when the perceived MD is heightened. Our analysis of 300 firms operating in China statistically confirms our hypotheses: first, under high MD, firms’ engagement in CSR results (...) in higher corporate legitimacy and competitive advantage, and second, their adherence to ethical business codes leads to higher corporate legitimacy. We conclude the article by outlining the implications for both theory and practice. (shrink)

Selective protein degradation maintains cellular homeostasis, but this process is disrupted in many diseases. Targeted protein degradation (TPD) approaches, built upon existing cellular mechanisms, are promising methods for therapeutically regulating protein levels. Here, we review the diverse palette of tools that are now available for doing so throughout the gene expression pathway and in specific cellular compartments. These include methods for directly removing targeted proteins via the ubiquitin proteasome system with proteolysis targeting chimeras (PROTACs) or dephosphorylation targeting chimeras (...) (DEPTACs). Similar effects can also be achieved through the lysosomal system with autophagy‐targeting chimeras (AUTACs), autophagosome tethering compounds (ATTECs), and lysosome targeting chimeras (LYTACs). Other methods act upstream to degrade RNAs (ribonuclease targeting chimeras; RIBOTACs) or transcription factors (transcription factor targeting chimeras; TRAFTACs), offering control throughout the gene expression process. We highlight the evolution and function of these methods and discuss their clinical implications in diverse disease contexts. (shrink)

The new possibility opened up by recent technology of ever-present, unbroken and potentially instant communication has had a fundamental effect on human relations, presenting us with modes of communication unprecedented in human history. Although there are some good effects, one of the bad effects is the potential for degradation in human relations in respect of the capacity for, and habit of, empathy, understanding and thoughtfulness between individuals, and an undermining of the expectation of reasonable anticipation in relation to others (...) and the consequent relief from the responsibility of having such anticipation. Many technological developments have changed human life. But one that so strongly determines communication, when communication is such a central part of what it means to be a person and to have relations with others, is bound to have far profounder effects than most other technological changes. The significance of new modes of communication is set against the fact that it is very recent and utterly unprecedented in human history, and is not something that could have been taken account of as part of the adaptations of human evolution. (shrink)

The Braess Paradox (BP) is a counterintuitive finding that degrading a network that is susceptible to congestion may decrease the equilibrium travel cost for each of its users. We illustrate this paradox with two networks: a basic network with four alternative routes from a single origin to a single destination, and an augmented network with six alternative routes. We construct the equilibrium solutions to these two networks, which jointly give rise to the paradox, and subject them to experimental testing. Our (...) purpose is to test the generality of the BP when the network is enriched as well as the effects of the information provided to the network users when they conclude their travel. To this end, we compare experimentally two information conditions when each of the two networks is iterated in time. Under public monitoring each user is accurately informed of the route choices and payoffs of all the users, whereas under private monitoring she is only informed of her own payoff. Under both information conditions, over iterations of the basic and augmented games, aggregate route choices converge to equilibrium. (shrink)

By posing the problem of the relation between the degradation of the environment and the market economy, one presupposes a preliminary answer to a more general question: As a result of his “instincts,” is man, by necessity, predatory upon the natural order which surrounds him? If the answer to this question were affirmative, the current massacre of the environment would, at best, represent no more than an acceleration of mechanisms which are as old as the emergence of man, and, (...) if the truth be told, any hope of the relationship between man and nature finding a new balance would be in vain. It is not very likely, however, that the answer would be a positive one. For one fundamental reason, nature is to a large extent a creation of man which has constantly modified itself throughout the history of man, ever since the invention of fire. What we call ‘nature’ is a structured, mobile complex of cycles which relate to our mineral environment and our living environment and which enable man to survive on earth; and it is impossible to ignore the action of man himself within these cycles. (shrink)

Probability logic studies the properties resulting from the probabilistic interpretation of logical argument forms. Typical examples are probabilistic Modus Ponens and Modus Tollens. Argument forms with two premises usually lead from precise probabilities of the premises to imprecise or interval probabilities of the conclusion. In the contribution, we study generalized inference forms having three or more premises. Recently, Gilio has shown that these generalized forms ``degrade'' -- more premises lead to more imprecise conclusions, i. e., to wider intervals. We distinguish (...) different forms of degradation. We analyse Predictive Inference, Modus Ponens, Bayes' Theorem, and Modus Tollens. Special attention is devoted to the case where the conditioning events have zero probabilities. Finally, we discuss the relation of degradation to monotonicity. (shrink)

Recent anxieties about the deterioration of the global environment have had the effect of intensifying the ambiguity that surrounds the social roles of scientists and engineers. This has happened not merely, as suggested at the outset, because the environmental crisis has made their roles more conspicuous. Nor is it merely because recent disasters have alerted us to new, or hitherto unrecognized, social consequences of using the latest science-based technologies. What also requires recognition is that ideas about the social role of (...) modern science and engineering are embedded in, hence mediated by, larger views of the world. Within such American worldviews, moreover, the status of science and engineering is closely bound up with their perceived effect upon the environment.In the dominant culture, accordingly, the respect given to scientists and engineers is in large measure dependent on their ability to play the central role assigned to them in the historical narrative about progress. As the ostensible heroes of that popular story, they are expected to lead the way in realizing the promise of prosperity and general well-being. The environmental crisis surely has diminished the credibility of that story, thereby causing the social role of science and engineering to seem more dubious — more ambiguous. To be sure, the crisis also may have the effect, for very different reasons, of increasing the power and responsibility of organized science. But the late twentieth-century task of damage control cannot possibly elicit anything like the respect accorded to organized science by the earlier belief in progress.It also is important to recall, finally, that the narrative of progress itself has undergone a disillusioning transformation. The early Enlightenment version of the story depicted scientists and engineers working in the service of a social and political ideal that all people could share. But the later technocratic concept of progress, with its sterile instrumentalist notion of advancing the power of science-based technology as an end in itself, is far less likely to inspire trust. Its patent inadequacies have had the effect of enhancing the appeal, if only by contrast, of the seemingly “anti-science” ideologies of pastoralism and primitivism. All of which might be taken to suggest that if the scientific and engineering professions want to recover some of the respect and status they once had, they would be well advised to join with sympathetic humanists and social scientists in recuperating some of the idealism that the project of modern science formerly derived from its place within the ideology of progress. That might entail the sacrifice of their technocratic posture of neutrality, dissociating themselves from people and institutions responsible for environmental degradation, and their help in formulating a new concept — which is to say, new criteria — of progress to which they might commit themselves. A primary test of any proposed social policy under this new dispensation surely would be whether it would improve, or at a minimum protect, the life-enhancing capacities of the global ecosystem. *** DIRECT SUPPORT *** A8402064 00011 *** DIRECT SUPPORT *** A8402064 00012 *** DIRECT SUPPORT *** A8402064 00013. (shrink)

Bill Bowring’s book attempts to argue for a Marxist account of international law that embraces it as a tool for progressive politics and revolutionary change. He argues it is necessary to give a substantive account of both, locating them in the real struggles of the oppressed. Specifically, he locates human rights in the three great revolutions ‐ the French, the Russian and the anticolonial. However, this revolutionary heritage has been ‘degraded’ by recent events. As such, it is necessary to adopt (...) ‘revolutionary conservatism’, invoking international law’s origins against its current degradation. This review argues that, owing to international law’s indeterminacy, Bowring’s project is susceptible to imperial appropriation. This means, however, that Bowring cannot give an account of why we should use international law. It then argues that Bowring’s account of Pashukanis is wrong, and that Pashukanis’s work can better make sense of Bowring’s insights and international law more generally. (shrink)

Matrix degradation and tissue remodelling directed by matrix‐degrading proteases are activated in physiological situations such as wound healing and involution of the prostate, ovaries and uterus. Recently, other activities, in addition to the cleavage of matrix proteins, have been attributed to matrix proteases including the release of growth factors from the extracellular matrix and roles in the maturation of adipocytes. This review describes extracellular proteases, including MMPs, plasminogen and cathepsins involved in the tissue remodelling processes that occur in the (...) breast during pubertal mammary development and the mammary cycle of pregnancy, lactation and weaning. It particularly focuses on development and weaning, termed mammary gland involution, when the majority of remodelling occurs. It also brings together recent findings on the exciting new functions of matrix‐degrading proteases. BioEssays 27:894–903, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Degradation of eukaryotic RNAs that contain premature termination codons (PTC) during nonsense‐mediated mRNA decay (NMD) is initiated by RNA decapping or endonucleolytic cleavage driven by conserved factors. Models for NMD mechanisms, including recognition of PTCs or the timing and role of protein phosphorylation for RNA degradation are challenged by new results. For example, the depletion of the SMG5/7 heterodimer, thought to activate RNA degradation by decapping, leads to a phenotype showing a defect of endonucleolytic activity of NMD (...) complexes. This phenotype is not correlated to a decreased binding of the endonuclease SMG6 with the core NMD factor UPF1, suggesting that it is the result of an imbalance between active (e.g., in polysomes) and inactive (e.g., in RNA‐protein condensates) states of NMD complexes. Such imbalance between multiple complexes is not restricted to NMD and should be taken into account when establishing causal links between gene function perturbation and observed phenotypes. (shrink)

This paper is organised in three interconnected parts. First, contemporary political economic approaches to understanding the structure of the global economic system are outlined and synthesised. Specifically, it is suggested that the current structural configuration of the globe is a transitional phase between the spatially-bounded configuration hypothesised by world-system theory and the configuration hypothesised by globalisation theorists. Second, the contemporary problem of environmental degradation is situated in a global structural context. Third, an outline and critique of Ulrich Beck 's (...) theory of the ' Risk Society ' is presented to illustrate the increasing inadequacy of nation-state-centric theories in explaining the dynamic linkage between global capitalism and local environmental degradation. (shrink)

This article analyses the new demographic programme that was announced by the Russian president, Vladimir Putin, in 2006. The main goal of this programme is to encourage fertility, especially the birth of a second child. New benefits should elevate the status of wome taking maternity leave, who might otherwise suffer from discrimination in the family. The housewife is considered to be dependent and `degraded'. We argue that this demographic politics recalls continuity with soviet gender politics centred on the support of (...) wage-earning working mothers. The programme provokes different critiques. Liberal critics argue that the programme is a populist one and it may have undesired economic and social consequences. Conservative critics want to encourage more traditional `woman' and `family' roles in society. Feminist critics argue that this politcs would reinforce both the inferior position of women on the labour market and gender imbalances on the symbolic level. (shrink)

The title is meant to emphasize the immense loss of status I take logic to have undergone in recent decades, and to suggest something about its causes. The loss is most obvious in the context of higher education, where almost no post-secondary institutions now have effectual general requirements in standard formal logic, as that was easily understood thirty or more years ago. Courses in so-called 'critical thinking' are, with rare and noble exceptions, only a further illustration of the point, for (...) many of them, if not most, say nothing at all about logical form and formal logic, and proceed as if thought and discourse could be critically understood and appraised in total ignorance of their formal aspects. (shrink)

This book discusses ethical behavior through the genocidal stages of the Holocaust. Paul E. Wilson first looks at the antisemitism in Germany and Europe beginning in the decades preceding the Nazis reign of terror, and goes on to discuss the ethical decisions made in the initial stages that moved society toward genocide. The author maintains that the stages of genocide represent subtle changes that can be happening within a society in response to the moral choices made by actors. By giving (...) attention to the stages of genocide in the Holocaust, this book contributes to the overall understanding of how the Holocaust was possible, and encourages the moral community to join the watch for the development of genocide in the modern world. (shrink)

High‐molecular‐weight hyaluronan acts as a ligand of the tumor‐suppressive Hippo signal, whereas degradation of hyaluronan from a high‐molecular‐weight form to a low‐molecular‐weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro‐oncogenic transcriptional coactivator yes‐associated protein (YAP), which creates a cancer‐predisposing microenvironment and drives neoplastic transformation of cells through both cell‐autonomous and non‐cell‐autonomous mechanisms. In fact, accumulation of low‐molecular‐weight hyaluronan in tissue stroma is observed in many types of cancers. Since inhibition of YAP activity suppresses tumor (...) growth in vivo, pharmacological intervention of the Hippo‐YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo‐YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors. (shrink)

Targeted protein degradation (TPD) has emerged as a highly promising approach for eliminating disease‐associated proteins in the field of drug discovery. Among the most advanced TPD technologies, PROteolysis TArgeting Chimera (PROTAC), functions by bringing a protein of interest (POI) into proximity with an E3 ubiquitin ligase, leading to ubiquitin (Ub)‐dependent proteasomal degradation. However, the designs of most PROTACs are based on the utilization of a limited number of available E3 ligases, which significantly restricts their potential. Recent studies have (...) shown that phytoplasmas, a group of bacterial plant pathogens, have developed several E3‐ and ubiquitin‐independent proteasomal degradation (UbInPD) mechanisms for breaking down host targets. This suggests an alternative approach for substrate recruitment and TPD. Here, we present existing evidence that supports the feasibility of UbInPD in eukaryotic cells and propose candidate proteins that can serve as docking sites for the development of E3‐independent PROTACs. (shrink)

The matrix‐degrading metalloproteinases are an intriguing family of enzymes that have evolved to digest specific extracellular matrix components. The expression of these enzymes is very highly regulated and can be controlled transcriptionally by a number of growth factors, tumor promoters, oncogenes, and hormones. It is suggested that the coordinated regulation of matrix metalloproteinases and their inhibitors by these agents modify the integrity of the extracellular matrix. These modifications may, at least in part, be responsible for mediating the effects of these (...) factors on complex physiological processes. (shrink)

Alzheimer's disease (AD) is a neurodegenerative disease exhibiting amyloid beta (Aβ) peptide accumulation as a key characteristic. Autophagy, which is dysregulated in AD, participates in the metabolism of Aβ. Unexpectedly, we recently found that autophagy, in addition to its degradative function, also mediates the secretion of Aβ. This finding adds Aβ to an increasing number of biomolecules, the secretion of which is mediated by autophagy. We also showed that inhibition of Aβ secretion through genetic deletion of autophagy leads to intracellular (...) Aβ accumulation, which enhanced neurodegeneration induced by autophagy deficiency. Hence, autophagy may play a central role in two pathological hallmarks of AD: Aβ amyloidosis and neurodegeneration. Herein, we summarize the role of autophagy in AD with focus on Aβ metabolism in light of the recently established role of autophagy in protein secretion. We discuss potential routes for autophagy‐mediated Aβ secretion and suggest experimental approaches to further elucidate its mechanisms. (shrink)

It is of fundamental importance to understand how the individual processes of gene expression, transcription, and translation, as well as mRNA and protein stability, act in concert to produce dynamic cellular proteomes. We use the concept of response times to illustrate the relation between degradation processes and responsiveness of the proteome to system changes and to provide supporting experimental evidence: proteins with short response times tend to be more strongly up‐regulated after 1 hour of TNFα stimulation than proteins with (...) longer response times. Furthermore, based on process‐dependent response times, we demonstrate that synthesis and degradation act in concert to enable rapid responses. Finally, by building on a previously published data set quantifying the mammalian gene expression cascade, we speculate on how combinations of stable and unstable mRNAs and proteins may be wired to transcriptional or translational regulation to support gene function. (shrink)

Visual information conveyed by iconic hand gestures and visible speech can enhance speech comprehension under adverse listening conditions for both native and non‐native listeners. However, how a listener allocates visual attention to these articulators during speech comprehension is unknown. We used eye‐tracking to investigate whether and how native and highly proficient non‐native listeners of Dutch allocated overt eye gaze to visible speech and gestures during clear and degraded speech comprehension. Participants watched video clips of an actress uttering a clear or (...) degraded (6‐band noise‐vocoded) action verb while performing a gesture or not, and were asked to indicate the word they heard in a cued‐recall task. Gestural enhancement was the largest (i.e., a relative reduction in reaction time cost) when speech was degraded for all listeners, but it was stronger for native listeners. Both native and non‐native listeners mostly gazed at the face during comprehension, but non‐native listeners gazed more often at gestures than native listeners. However, only native but not non‐native listeners' gaze allocation to gestures predicted gestural benefit during degraded speech comprehension. We conclude that non‐native listeners might gaze at gesture more as it might be more challenging for non‐native listeners to resolve the degraded auditory cues and couple those cues to phonological information that is conveyed by visible speech. This diminished phonological knowledge might hinder the use of semantic information that is conveyed by gestures for non‐native compared to native listeners. Our results demonstrate that the degree of language experience impacts overt visual attention to visual articulators, resulting in different visual benefits for native versus non‐native listeners. (shrink)

In this book, Carey gives cognitive science a detailed account of the origins of concepts and an explanation of how origins stories are essential to understanding what concepts are and how we use them. At the same time, this book's details help highlight the challenge of explaining how conceptual change works with real-world concepts that often have heavily degraded internal content.

Espace d'expression et de discussion, les forums médiatiques font se rencontrer des individus aux opinions et appartenances variées. Il s'agit d'observer le rôle du dispositif communicationnel et la manière dont ses membres en usent: privilégient-ils la dimension conversationnelle ou publicitaire? quelle est la nature de cet espace public et des échanges qui s'y déroulent? L'analyse statistique et de contenu des courriels révèle un espace interactionnel de groupe où la publicité l'emporte sur la sociabilité, ainsi qu'une parole publique dégradée marquée par (...) l'incommunication et une dérive ethniciste.Space for expression and discussion forums are media meet individuals with varied opinions and affiliations. It is to observe the role of communicative device and how its members wear: they prefer the conversational dimension or advertising? What is the nature of public space and exchanges that take place? Statistical analysis and content of emails reveals a group interactional space where advertising outweighs sociability, and a degraded public speech marked by miscommunication and a drift ethnocentric. (shrink)

In this paper I argue that the value attributed to coral reefs drives the characterisation of evidence for their regeneration or degradation. I observe that regeneration and degradation depend on an understanding of what an ecosystem looks like when undegraded (a baseline), and that many mutually exclusive baselines can be given for any single case. Consequently, facts about ecological processes are insufficient to usefully and non-arbitrarily characterise changes to ecosystems. By examining how baselines and the value of reefs (...) interact in coral and algal reef examples, I argue that considering the value of an ecosystem is a necessity when describing processes like regeneration and degradation. This connects value as studied in socio-ecological and economic research with values as discussed in the philosophy of science literature. It also explains why such a broad range of processes may be considered regenerative, including those which introduce significant novelty, as well as pointing towards ways to mediate related debates, such as those surrounding novel and ‘pristine’ ecosystems. (shrink)

There is no corporal philosophy at the level of other philosophical subdisciplines. A research line has begun whose ultimate goal is to determine whether a somatic philosophy can be built. From a pragmatist and biopolitical approach, the present study investigated why it has not been possible to develop grounded somatic philosophy. As an answer, the “idealist–dualist episteme” is described, which encompasses invariants in the history of idealist philosophy at the ontological, gnoseological, ethical–political, and pedagogical levels. These constants reflect somatophobia, as (...) well as an ontological and gnoseological disregard of the body, which has led to the irrelevance of the body and corporeality in philosophy until the arrival of the “bodily turn”. The critique of this prevailing idealism and dualism will enable a review of current approaches based on these positions, such as embodiment, enactivism, embodied cognition, or embodied artificial intelligence. It opens up a new philosophical line with a universalis scope that is open to the eclectic construction of a pragmatic corporal philosophy that takes into account Chinese, Japanese, or African philosophies. (shrink)

Ultra-high-performance concrete (UHPC) is gaining popularity due to its superior mechanical properties, including high strength, toughness, durability, and excellent seismic performance. However, the risk of explosive spalling in UHPC structures exposed to fire poses a significant challenge, fundamentally hindering comprehensive studies on fire safety and limiting the broader engineering applications of UHPC. In this study, the mixture proportion of UHPC was developed and optimized by comparing the usage of yellow river and standard sands, different types of chemical admixtures, and different (...) curing regimes. Furthermore, a sensitive case study was also conducted to optimize the calcined bauxite content to improve UHPC's fire resistance. For these purposes, 189 UHPC cubes, incorporating variations in particle types, superplasticizer types, and curing regimes, were tested under three thermal levels, such as 200℃,400℃, and 600℃. The microstructural evolution of heated cube specimens was then observed using a scanning electron microscope (SEM) examination. Calcined bauxite was then considered to replace the standard sand to improve the fire resistance of UHPC and enhance the residual compressive strength of cube specimens under thermal conditions. For this purpose, 0%, 20%, 40%, 60%, 80%, and 100% calcined bauxite content was designed as six case studies. Furthermore, the degradation of UHPC strength was also investigated for the corresponding six case studies by conducting the uniaxial compressive experiments. Finally, the microstructural evolution under both thermal conditions and calcined bauxite content was observed and discussed. (shrink)

The performance of most of the state-of-the-art speaker recognition systems deteriorates under degraded conditions, owing to mismatch between the training and testing sessions. This study focuses on the front end of the speaker verification system to reduce the mismatch between training and testing. An adaptive voice activity detection algorithm using zero-frequency filter assisted peaking resonator was integrated into the front end of the SV system. The performance of this proposed SV system was studied under degraded conditions with 50 selected speakers (...) from the NIST 2003 database. The degraded condition was simulated by adding different types of noises to the original speech utterances. The different types of noises were chosen from the NOISEX-92 database to simulate degraded conditions at signal-to-noise ratio levels from 0 to 20 dB. In this study, widely used 39-dimension Mel frequency cepstral coefficient features were used, and Gaussian mixture model–universal background model was used for speaker modeling. The proposed system’s performance was studied against the energy-based VAD used as the front end of the SV system. The proposed SV system showed some encouraging results when EMD-based VAD was used at its front end. (shrink)

Many human rights charters contain prohibitions on inhuman and degrading treatment of prisoners and detainees. Terms like “inhuman” and “degrading” are difficult to interpret, but they are certainly not meaningless. It is important to attend to attend to the meanings of the words themselves, as well as to the decisions that courts have made about particular practices. Reflection on the meanings of these highly-charged terms reveals important complexity, which we can unpack in a way that enables us to better focus (...) our debate about the proper treatment of prisoners and detainees. Focusing on the ordinary-language meaning of evaluative terms like “inhuman” and “degrading” also helps us approach the relation between rules and standards in law more thoughtfully, as we see why it is important not to let the evaluative meaning of these terms be superseded by the definitions established in the course of their application. (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)