What does it mean to ‘drop out’ of therapy? Many definitions of ‘dropout’ have been proposed, but the most widely accepted is the client ending treatment without agreement of their therapist. However, this is in some ways an external criterion that does not take into account the client’s experience of therapy, or reasons for ending it prematurely. This study aimed to identify whether there were more meaningful categories of dropout than the existing dropout definition, and to test whether this refined (...) categorisation of dropout was associated with clinical outcomes. This mixed-methods study used a subset of data from the IMPACT trial, which investigated psychological therapies for adolescent depression. Adolescents were randomly allocated to a treatment arm (Brief Psychosocial Intervention; Cognitive-Behavioural Therapy; Short-Term Psychoanalytic Psychotherapy). The sample for this study comprised 99 adolescents, aged 11-17 years. 32 were classified as having dropped out of treatment and participated in post-therapy qualitative interviews about their experiences of therapy. For 26 dropout cases, the therapist was also interviewed. 67 cases classified as having completed treatment were included to compare their outcomes to dropout cases. Interview data for dropout cases were analysed using ideal type analysis. Three types of dropout were constructed: ‘dissatisfied’ dropout, ‘got-what-they-needed’ dropout, and ‘troubled’ dropout. ‘Dissatisfied’ dropouts reported stopping therapy because they did not find it helpful. ‘Got-what-they-needed’ dropouts reported stopping therapy because they felt they had benefitted from therapy. ‘Troubled’ dropouts reported stopping therapy because of a lack of stability in their lives. The findings indicate the importance of including the perspective of clients in definitions of drop out, as otherwise there is a risk that the heterogeneity of 'dropout' cases may mask more meaningful distinctions. Clinicians should be aware of the range of issues experienced by adolescents in treatment that lead to disengagement. Our typology of dropout may provide a framework for clinical decision-making in managing different types of disengagement from treatment. (shrink)

_Objective:_ The aim of the current study was to investigate associations, unique and interactive, between mothers’ and children’s histories of childhood sexual abuse (CSA) and children’s psychiatric outcomes using an intergenerational perspective. Further, we were particularly interested in examining whether maternal reflective functioning about their own trauma (T-RF) was associated with a lower likelihood of children’s abuse exposure (among children of CSA-exposed mothers). _Methods:_ One hundred and eleven children ( M age = 9.53 years; 43 sexual abuse victims) and their (...) mothers ( M age = 37.99; 63 sexual abuse victims) participated in this study. Mothers completed the Parent Development Interview (PDI), which yielded assessments of RF regarding their own experiences of abuse, and also reported on their children’s internalizing and externalizing symptoms. _Results:_ Children of CSA-exposed mothers were more likely to have experienced CSA. A key result was that among CSA-exposed mothers, higher maternal T-RF regarding their own abuse was associated with lower likelihood of child CSA-exposure. Mothers’ and children’s CSA histories predicted children’s internalizing and externalizing symptoms, such that CSA exposure for mother or child was associated with greater symptomatology in children. _Conclusion:_ The findings show that the presence of either maternal or child CSA is associated with more child psychological difficulties. Importantly in terms of identifying potential protective factors, maternal T-RF is associated with lower likelihood of CSA exposure in children of CSA-exposed mothers. We discuss these findings in the context of the need for treatments focusing on increasing T-RF in mothers and children in the context of abuse to facilitate adaptation and reduce the intergenerational risk. (shrink)

Modern science is increasingly focused on research that solves specific technological problems. In the world literature there are different, but generally similar, names for such studies. For example, German and Russian researchers use the term «problem-oriented research», the names «mission-oriented research», research as a response to «great challenges» and «frontier research», «science mode 2» are also used. In Ukraine, particularly in the National Academy of Sciences of Ukraine, the name «targeted research programs» and «targeted scientific (scientific and technical) projects» are (...) used. The article analyzes features of targeted research and the status of the obtained knowledge. It emphasizes their direct involvement in the social sphere — economic, political, social relations in general, because they are the basis of modern technology and their development is interested in the general public — producers and consumers of material goods. The knowledge obtained in these studies is knowledge «to order», which requires a solution to the relationship between basic and applied research, the principles of professional activity of scientists, «academic freedoms», changes in epistemological, socio-humanitarian principles of science as a social institution. In the professional activity of a scientist, the praxeologization of science requires an orientation on the humanity of the produced knowledge, which, in fact, is a combination of knowledge about nature with knowledge about human. In this case, the scientist must be an expert in related disciplines. The organizers of targeted research solve this situation through the collective implementation of research, or, as expressed by R. Florida, the use of «social intelligence». At the same time, the latter requires from the scientist, as a specialist, not only purely professional competencies but also individual psychological skills of work (creativity) in an interdisciplinary team (mutual assistance, tolerance, empathy, etc.) and interaction with the transdisciplinary community. Otherwise, the profession of a scientist becomes socially engaged in terms of competencies and activities, and the leader in the research team performs moderative rather than directive functions. Although targeted research programs are becoming widespread, leading in solving urgent practical problems, but in the scientific field, a balance must be maintained between research «to order» and research that will be the basis for future development of science and society. (shrink)

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, (...) it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

(2002). 'Target Approval Delays Cost Air Force Key Hits': Law, Policy, Ethics and the Warfighter's Dilemma. Journal of Military Ethics: Vol. 1, No. 2, pp. 113-124.

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 nineteenth-century strategist Carl von Clausewitz describes “fog” and “friction” as fundamental features of war. Military leverage of sophisticated information technology in the twenty-first century has improved some tactical operations but has not lifted the fog of war, in part, because the means for reducing uncertainty create new forms of it. Drawing on active duty experience with an American special operations task force in Western Iraq from 2007 to 2008, this article traces the targeting processes used to “find, fix, and (...) finish” alleged insurgents. In this case they did not clarify the political reality of Anbar province but rather reinforced a parochial worldview informed by the Naval Special Warfare community. The unit focused on the performance of “direct action” raids during a period in which “indirect action” engagement with the local population was arguably more appropriate for the strategic circumstances. The concept of “data friction”, therefore, can be understood not simply as a form of resistance within a sociotechnical system but also as a form of traction that enables practitioners to construct representations of the world that amplify their own biases. (shrink)

Though dividing one’s attention between two input streams typically impairs performance, detecting a behaviorally relevant stimulus can sometimes enhance the encoding of unrelated information presented at the same time. Previous research has shown that selection of this kind boosts visual cortical activity and memory for concurrent items. An important unanswered question is whether such effects are reflected in processing quality and functional connectivity in visual regions and in the hippocampus. In this fMRI study, participants were asked to memorize a stream (...) of naturalistic images and press a button only when they heard a predefined target tone. Images could be presented with a target tone, with a distractor tone, or without a tone. Auditory target detection increased activity throughout the ventral visual cortex but lowered it in the hippocampus. Enhancements in functional connectivity between the ventral visual cortex and the hippocampus were also observed following auditory targets. Multi-voxel pattern classification of image category was more accurate on target tone trials than on distractor and no tone trials in the fusiform gyrus and parahippocampal gyrus. This effect was stronger in visual cortical clusters whose activity was more correlated with the hippocampus on target tone than on distractor tone trials. In agreement with accounts suggesting that subcortical noradrenergic influences play a role in the attentional boost effect, auditory target detection also caused an increase in locus coeruleus activity and phasic pupil responses. These findings outline a network of cortical and subcortical regions that are involved in the selection and processing of information presented at behaviorally relevant moments. (shrink)

The title of this book echoes a phrase used by the Washington Post to describethe American attempt to kill Saddam Hussein at the start of the war againstIraq. Its theme is the notion of targeting (skopos) as the name of an intentionalstructure in which the subject tries to confirm its invulnerability by aiming todestroy a target. At the center of the first chapter is Odysseus’s killing of the suitors;the second concerns Carl Schmitt’s Roman Catholicism and Political Form; thethird and fourth (...) treat Freud’s “Thoughts for the Times on War and Death” and“The Man Moses and Monotheistic Religion.” Weber then traces the emergenceof an alternative to targeting, first within military and strategic thinking itself(“Network Centered Warfare”), and then in Walter Benjamin’s readings of“Capitalism as Religion” and “Two Poems of Friedrich Hölderlin.”. (shrink)

We consider the problem of choosing the location of a public facility either (a) on a tree network or (b) in a Euclidean space. (a) (1996) characterize the class of target rules on a tree network by Pareto efficiency and population-monotonicity. Using Vohra's (1999) characterization of rules that satisfy Pareto efficiency and replacement-domination, we give a short proof of the previous characterization and show that it also holds on the domain of symmetric preferences. (b) The result obtained for model (a) (...) proves to be crucial for the analysis of the problem of choosing the location of a public facility in a Euclidean space. Our main result is the characterization of the class of coordinatewise target rules by unanimity, strategy-proofness, and either replacement-domination or population-monotonicity. (shrink)

The controversy surrounding targeted killings represents a crisis of conscience for policymakers, lawyers, philosophers and leading military experts grappling with the moral and legal limits of the war on terror. The book examines the legal and philosophical issues raised by government efforts to target suspected terrorists without giving them the safeguards of a fair trial.

MYC is a transcription factor, which not only directly modulates multiple aspects of transcription and co‐transcriptional processing (e.g. RNA‐Polymerase II initiation, elongation, and mRNA capping), but also indirectly influences several steps of RNA metabolism, including both constitutive and alternative splicing, mRNA stability, and translation efficiency. As MYC is an oncoprotein whose expression is deregulated in multiple human cancers, identifying its critical downstream activities in tumors is of key importance for designing effective therapeutic strategies. With this knowledge and recent technological advances, (...) we now have multiple angles to reach the goal of targeting MYC in tumors, ranging from the direct reduction of MYC levels, to the dampening of selected house‐keeping functions in MYC‐overexpressing cells, to more targeted approaches based on MYC‐induced secondary effects. (shrink)

The role of membrane receptors is regarded as being to transduce the signal represented by ligand binding from the external cell surface across the membrane into the cell. Signals are subsequently conveyed from the cytoplasm to the nucleus through a combination of second-messenger molecules, kinase/phosphorylation cascades, and transcription factor (TF) translocation to effect changes in gene expression. Mounting evidence suggests that through direct targeting to the nucleus, polypeptide ligands and their receptors may have an important additional signaling role. Ligands such (...) as those of the platelet-derived and fibroblast growth factor classes, as well as cytokines such as interferon-γ and interleukins-1 and -5, have been found to localize in the nucleus through the action of nuclear localization sequences (NLSs). Where tested, these NLSs appear to be essential for full signaling activity and may be responsible for cotranslocating receptors to the nucleus in complexes with their ligands. The implication is that, subsequent to endocytosis at the membrane, particular polypeptide ligands or their receptors, or both, may translocate to the nucleus to participate directly in gene regulation. BioEssays 20:400–411, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Three experiments investigated the role of target-target perceptual similarity within the attentional blink. Various geometric shapes were presented in a rapid serial visual presentation task. Targets could have 2, 1, or 0 shared features. Features included shape and size. The second target was presented after five or six different lags after the first target. The task was to detect both targets on each trial. Second-target report accuracy was increased by target-target similarity. This modulation was observed more for mixed-trial (...) design as compared with blocked design. Results are discussed in terms of increased stability of working memory representations and reduced interference for second-target processing. (shrink)

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target‐the‐weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed (...) tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target‐the‐weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. (shrink)

There are important ethical issues to be examined before launching any public health intervention, particularly when targeting vulnerable groups. The aim of this article is to identify and discuss ethical concerns that may arise when intervening for health behavior change among adolescents identified as overweight. These concerns originate from an intervention designed to capacitate adolescents to increase self-determined physical activity. Utilizing an ethical framework for prevention of overweight and obesity, we identified three ethical aspects as particularly significant: the attribution of (...) responsibility for health behavior, liberty to choose, and the effect on the participants’ psychosocial well-being. It is discussed whether and how measures can be taken to deal with these aspects. It seems evident that the ethical aspects are mainly concerned with the vulnerability of adolescents identified as overweight. However, we claim that when individual feedback and counseling is provided, tailored interventions have a unique potential to empower adolescents to make ethically anchored decisions about their own health behavior. (shrink)

Regulated secretory proteins are stored within specialized vesicles known as secretory granules. It is not known how proteins are sorted into these organelles. Regulated proteins may possess targeting signals which interact with specific sorting receptors in the lumen of the trans‐Golgi network (TGN) prior to their aggregation to form the characteristic dense‐core of the granule. Alternatively, sorting may occur as the result of specific aggregation of regulated proteins in the TGN. Aggregates may be directed to secretory granules by interaction of (...) a targeting signal on the surface with a sorting receptor. Novel targeting signals which confer on regulated proteins a tendency to aggregate under certain conditions, and in so doing cause them to be incorporated into secretory granules, have been implicated. Specific targeting signals may also play a role in directing membrane proteins to secretory granules. (shrink)

In the literature on linguistic context-sensitivity, a recurrent move has been made with the intention of attacking Charles Travis's occasion-sensitivity. The move is to provide a semantic analysis of the meaning of an expression which makes the content of that expression context sensitive but without providing any reason to think that the meaning of the expression is a character. I argue that this move is off-target. Such proposals are entirely consistent with occasion-sensitivity and so don't constitute an attack on it.

The role of membrane receptors is regarded as being to transduce the signal represented by ligand binding from the external cell surface across the membrane into the cell. Signals are subsequently conveyed from the cytoplasm to the nucleus through a combination of second-messenger molecules, kinase/phosphorylation cascades, and transcription factor (TF) translocation to effect changes in gene expression. Mounting evidence suggests that through direct targeting to the nucleus, polypeptide ligands and their receptors may have an important additional signaling role. Ligands such (...) as those of the platelet-derived and fibroblast growth factor classes, as well as cytokines such as interferon-γ and interleukins-1 and -5, have been found to localize in the nucleus through the action of nuclear localization sequences (NLSs). Where tested, these NLSs appear to be essential for full signaling activity and may be responsible for cotranslocating receptors to the nucleus in complexes with their ligands. The implication is that, subsequent to endocytosis at the membrane, particular polypeptide ligands or their receptors, or both, may translocate to the nucleus to participate directly in gene regulation. BioEssays 20:400–411, 1998.© 1998 John Wiley & Sons Inc. (shrink)

From the daily life, how to get the access to philosophy, what is the approaches to philosophy? Regarding the big topics /big affair in the world, are they related to the philosophy? what and how shall the philosophy do? About some concept, word, have we already fully confirmed their meaning? What shall the philosophy do to make their meaning clear and confirmed? Refers to the philosophy itself, have we already confirmed its study object? What is Philosophy? what is the main (...) study object for the philosophy? It is the pity that till now, for the whole world philosophy field, the main study object for the philosophy have not been confirmed. There are various kinds of answer, this means philosophy, from the past one hundred years, till now, has not work out the state of downturn and confusion.Since the philosophy itself is not clear, then no wonder from the late of 19 century to now, philosophy seems did litting achievement for the human being, for the civilization, for the progress, its glory looks gray, compared with Science, which is in fact born by philosophy although. So, before the philosophy could work well for the civilization, firstly, we should make the philosophy clear, confirm the main object of philosophy, target the correct object for philosophy! Only after this first work, we could expect philosophy do well on its tasks and function. For my this paper, its essential point is to present an answer for the target object belongs to the philosophy. Through demonstrate as per scientific logic and philosophy’s whole history, this answer, namely, the only target object belongs to philosophyis the Ontology and Cognition. Let philosophy go back to its correct place, its correct way. Then, it could move ahead. only after we get new progress on the study of Ontology and Cognition, and with the help of this new achievement of Ontology and Cognition, we can get progress on the study of the fields related to the human being and progress of civilization. As far as what is the Ontology and Cognition, which kind new achievement of Ontology and Cognition we couldexpect, that is the next step. (shrink)

Targeted hypermutation has proven to be a useful survival strategy for bacteria under severe stress and is also used by multicellular organisms in specific instances such as the mammalian immune system. This might appear surprising, given the generally observed deleterious effects of poor replication fidelity/high mutation rate. A previous theoretical model designed to explore the role of replication fidelity in the origin of life was applied to a simulated hypermutation scenario. The results confirmed that the same model is useful for (...) analyzing hypermutation and can predict the effects of the same parameters (survival probability, replication fidelity, mutation effect, and others) on the survival of cellular populations undergoing hypermutation as a result of severe stress. (shrink)

Apoptotic pathways have always been regarded as a key‐player in preserving tissue and organ homeostasis. Excessive activation or resistance to activation of cell death signaling may indeed be responsible for several mechanisms of disease, including malignancy and chronic degenerative diseases. Therefore, targeting apoptotic factors gained more and more attention in the scientific community and novel strategies emerged aimed at selectively blocking or stimulating cell death signaling. This is also the case for the TMEM219 death receptor, which is activated by a (...) circulating ligand, the Insulin‐like growth factor binding protein 3 (IGFBP3) and induces a caspase‐8‐dependent apoptosis of the target cells. Interestingly, stimulation of the IGFBP3/TMEM219 axis exerts an anti‐proliferative effect, while blockade of the TMEM219 deleterious signal protects TMEM219‐expressing cells of the endocrine pancreas, lung, and intestine from damage and death. Here, we summarize the most updated reports on the role of the IGFBP3/TMEM219 apoptotic axis in disease conditions, including intestinal disorders and diabetes, and we describe the advancements in designing and testing novel TMEM219‐based targeting approaches in emerging potential clinical applications. (shrink)

In this book, Leonard Talmy proposes that a single linguistic/cognitive system, targeting, underlies two domains of linguistic reference, those termed anaphora and deixis. Talmy argues that language engages the same cognitive system to single out referents whether they are speech-internal or speech-external. Talmy explains the targeting system in this way: as a speaker communicates with a hearer, her attention is on an object to which she wishes to refer; this is her target. To get the hearer's attention on it as (...) well, she uses a trigger -- a word such as this, that, here, there, or now. The trigger initiates a three-stage process in the hearer: he seeks cues of ten distinct categories; uses these cues to determine the target; and then maps the concept of the target gleaned from the cues back onto the trigger to integrate it into the speaker's sentence, achieving comprehension. The whole interaction, Talmy explains, rests on a coordination of the speaker's and hearer's cognitive processing. The process is the same whether the referent is anaphoric or deictic. Talmy presents and analyzes the ten categories of cues, and examines sequences in targeting, including the steps by which interaction leads to joint attention. A glossary defines the new terms in the argument. (shrink)

ABSTRACTThis article assesses whether the contemporary consensus of just war thinking to allow only for defence as just cause for war between states should also be applied to the practice of target...

Consistent with the target article, recent evidence indicates that the superior colliculus (SC) is somehow involved in target selection. However, it is not yet known whether this function is inherent to the SC or inherited from its inputs, how the selection process occurs for different movements, or how target selection by the SC is related to covert selection (i.e., attention). (Published Online May 1 2007).

The federal government is funding a sea change in health care by investing in interventions targeting social determinants of health, which are significant contributors to illness and health inequity. This funding power has encouraged states, professional and accreditation organizations, health care entities, and providers to focus heavily on social determinants. We examine how this shift in focus affects clinical practice in the fields of oncology and emergency medicine, and highlight potential areas of reform.

While much emphasis is placed on the need to improve critical thinking (CT) among college students (Abrami, Bernard, Borokhovski, Wade, Surkes, Tamim, & Zhang, 2008, p. 1102), few studies describe precise methodologies for doing so (Behar-Horenstein & Niu, 2011, p. 36) and even fewer identify improvements in CT dispositions as a desired course outcome (Perkins, Tishman, Ritchhart, Donis, & Andrade, 2000, p. 288). This study attempts to fill a gap in the studies of CT methodologies aimed at improving CT dispositions. (...) In this study, 78 community college students enrolled in a CT course that emphasized targeted CT interventional strategies. The students took the California Critical Thinking Dispositions Inventory (CCTDI) as a pre-test and as a post-test. Results indicate that the targeted instruction significantly influenced overall scores, as well as four of the seven subscale categories. (shrink)

This chapter discusses outlines key debates about the range of legitimate targets in war.

Proteolysis-targeting chimeric molecules represent an emerging technique that is receiving much attention for therapeutic intervention. The mechanism is based on the inhibition of protein function by hijacking a ubiquitin E3 ligase for protein degradation. The hetero-bifunctional PROTACs contain a ligand for recruiting an E3 ligase, a linker, and another ligand to bind with the protein targeted for degradation. Thus, PROTACs have profound potential to eliminate “undruggable” protein targets, such as transcription factors and non-enzymatic proteins, which are not limited to (...) physiological substrates of the ubiquitin-proteasome system. These findings indicate great prospects for PROTACs in the development of therapeutics. However, there are several limitations related to poor stability, biodistribution, and penetrability in vivo. This review provides an overview of the main PROTAC-based approaches that have been developed and discusses the promising opportunities and considerations for the application of this technology in therapies and drug discovery. The hetero-bifunctional PROTAC molecules contain a ligand for recruiting an E3 ligase linked with a ligand to bind with the protein targeted for degradation. Thus, PROTACs have profound potential to eliminate “undruggable” disease-causing proteins, which are not limited to physiological substrates of the ubiquitin-protease system, suggesting great prospects for therapeutic development. (shrink)

Mice with alterations to specific endogenous genes can be produced by gene targeting in embryonic stem cells. The field has developed rapidly over the past decade, so that large numbers of mice with different gene deficiencies have been generated. Knockout mice provide an ideal opportunity to analyse the function of individual mammalian genes and to model a range of human inherited disorders. This powerful approach has also identified numerous examples of gene redundancy and has highlighted the need to consider metabolic (...) differences between man and mouse in disease modelling. More sophisticated gene‐targeting methods are now being used to introduce subtle gene alterations. In the future, more refined genetic analysis and genome, rather than individual gene, alterations will be achieved by incorporating site‐specific recombination into targeting strategies. Gene targeting could also make a contribution to improved protocols for gene therapy. (shrink)

Smart MR contrast agents exhibit modulation of their relaxivity by specific physiological or biochemical trigger-events, while targeted MR contrast agents are envisioned to deliver the large gadolinium chelates into the target tissue. In an effort to develop novel smart and targeted MR contrast agents, the series of the DO3A based multifunctional chelating agents with the variable length of the side chain has been synthesized. They serve as valuable multipurpose precursors for contrast agents based on gadolinium chelates in the design of (...) relaxometric MR probes. The presence of the amino group in the side chain of the macrocycle allows for conversion into various functional groups (aminophosponates, aminocarboxylates, etc.) or for conjugation with different biomolecules, dyes, and polymers. Choice of the functional groups depends on the.. (shrink)

Known terrorists are often targeted for death by the governments of Israel and the United States. Several thousand have been killed by drones or by operatives on the ground in the last twenty years. Is this form of killing justified? Is there anything about it that should disturb us? In this for-and-against book, political theorists Jeremy Waldron and Tamar Meisels engage in extended debate to illuminate these issues. They consider the actions of targeting and hunting down named individuals, and they (...) address concerns about the possibility of this practice getting out of hand and being extended beyond the realm of counter-terrorism. (shrink)

The purpose of this case study is to investigate the identity linguistically and cognitively presented by official Target Corporation’s discourse and to unveil any structures or elements that are prominent enough to be included in the employees’ discourse production. The assumption is that the particular language we speak and the structures we choose in various contexts predispose us to think and act in certain ways. As for the approach utilized in this research, it is rather data-driven than data-based. Methods of (...) Critical Discourse Analysis are employed and they are supplemented by Critical Metaphor Analysis. The sampling of the customers was opportunistic. The identity in and around organization can be effectively investigated through linguistic methods. The study has shown that the vision of the company’s identity is more integrated by the executives and team leaders than grassroots employees. The paper draws attention to the very basic level of communication and its potential of imposing certain conceptualizations – the actual building blocks of any narrative. Moreover, the methodology employed goes beyond mere content analysis and applies rigorous linguistic analysis of company discourse. (shrink)

We examine whether and when socially oriented shareholder activists use firms’ corporate social performance (CSP) to identify them as attractive targets for their activism. We build on the research in social movements theory and stakeholder theory to theorize how firms’ engagement with primary and secondary stakeholders reflected in their technical and institutional CSP respectively allows socially oriented shareholder activists to identify targets. We develop a theoretical model by identifying corporate targets’ degree of (1) receptivity to and (2) (...) need to comply with activist demands as two key dimensions of their corporate opportunity structure that explains the variance in firms’ attractiveness as targets for activist demands. We show that a firm’s technical and institutional CSP independently affect the likelihood of activists targeting the firm. We also show that our model has greater explanatory power at firms with high resource slack and from activists not identifying as socially responsible investment funds. Analysis of CSP and shareholder proposals data of 992 U.S. public firms over an 8-year window of observation largely supports our theory. (shrink)

The purpose of this paper is the analysis of both legal and ethical ways of justifying targeted killings. I compare two legal models: the law enforcement model vs the rules of armed conflicts; and two ethical ones: retribution vs the right of self-defence. I argue that, if the targeted killing is to be either legally or ethically justified, it would be so due to fulfilling of some criteria common for all acceptable forms of killing, and not because terrorist activity is (...) somehow distinguished and gives special privileges to a state that fights it. The practical implication of my analysis is that one of the most spectacular targeted killings, which was the targeting and killing of Osama bin Laden in May 2011, was not justified, because it was only supposed to be a retribution for the September 11th terrorist attacks. (shrink)

As Nelson Goodman highlighted, there are two main senses of “abstract” that can be found in discussions about abstract art. On the one hand, a representation is abstract if it leaves out certain features of its target. On the other hand, something can be abstract to the extent that it does not represent a concrete subject. The first sense of “abstract” is well-known in philosophy of science. For example, philosophers discuss mathematical models of physical, biological, and economic systems as being (...) abstract in this sense. However, it is the second sense that dominates discussions of abstract art in aesthetics. For example, abstract art was (and is) considered revolutionary precisely for being non-figurative. Through an analysis of artists including Kandinsky, Malevich, and Mondrian, we develop a reading of this second sense, which we call “generative abstraction,” as opposed to “subtractive” abstraction. Generative abstraction is a process in which a new artifact is created which does not represent the initial concrete target system that inspired it (if there was one), where the artifact’s features are explored for their own sake, and where the “language” of the new artifact is in some way more “universal.” Focusing on this sense of abstraction is helpful in revealing the complexity of the process of crafting an abstract artifact, in problematizing the notion that abstraction can always be un-done (or concretized), as well as revealing new ways for abstractions to be epistemically (un)successful. (shrink)

Given a target area and a location-aware social network, the location-aware influence maximization problem aims to find a set of seed users such that the information spread from these users will reach the most users within the target area. We show that the problem is NP-hard and present an approximate algorithm framework, namely, TarIM-SF, which leverages on a popular sampling method as well as spatial filtering model working on arbitrary polygons. Besides, for the large-scale network we also present a coarsening (...) strategy to further improve the efficiency. We theoretically show that our approximate algorithm can provide a guarantee on the seed quality. Experimental study over three real-world social networks verified the seed quality of our framework, and the coarsening-based algorithm can provide superior efficiency. (shrink)

While mass spectrometry (MS)‐based quantification of small molecules has been successfully used for decades, targeted MS has only recently been used by the proteomics community to investigate clinical questions such as biomarker verification and validation. Targeted MS holds the promise of a paradigm shift in the quantitative determination of proteins. Nevertheless, targeted quantitative proteomics requires improvisation in making sample processing, instruments, and data analysis more accessible. In the backdrop of the genomic era reaching its zenith, certain questions arise: is the (...) proteomic era about to come? If we are at the beginning of a new future for protein quantification, are we prepared to incorporate targeted proteomics at the benchside for basic research and at the bedside for the good of patients? Here, an overview of the knowledge required to perform targeted proteomics as well as its applications is provided. A special emphasis is placed on upcoming areas such as peptidomics, proteoform research, and mass spectrometry imaging, where the utilization of targeted proteomics is expected to bring forth new avenues. The limitations associated with the acceptance of this technique for mainstream usage are also highlighted. (shrink)

Christine Swanton presents a new target centred virtue ethics, which is opposed to orthodox virtue ethics in two major ways. She rejects the 'natural goodness' metaphysics of neo-Aristotelian virtue ethics in favour of a 'hermeneutic ontology' of ethics, and she offers a new target centred framework for assessing rightness of acts.

This volume analyzes welfare policies by looking at the making of their target publics. It examines how these populations are identified and constructed by policy making. The contributors apply the classic theoretical question about who gets what, when, and how, but also suggest the revisiting of policy-feedback analysis. Coverage includes empirical case studies in different geographical areas. It looks at Europe, the United States and also considers Mayotte, set in a post-colonial context. The chapters also examine different aspects of welfare, (...) including the bureaucratic treatment of marginalized populations as well as the middle class. The authors draw on diverse conceptual approaches and investigative methodologies. They conduct participant observation in public or nonprofit organizations, explore administrative records, and interview actors at various stages of policymaking. This qualitative material is then combined with relevant quantitative data. Readers are guided through a multilevel approach of welfare policies, from their definition to their implementation. They gain insight into the targeting of publics, from the higher reaches of government to the most underprivileged groups of the social world. Overall, the book compares different national contexts and social policy fields. This approach unearths regularities, enabling the authors to reassess major contemporary transformations of the welfare State. (shrink)

This paper investigates Neoplatonist literary criticism by framing the special interest in the target of each dialogue within the context of cosmo-literary theory. The starting hypothesis is that the themes of Plato's dialogues do not fully meet the expectations of a new didactics based on isagogical schemes as an image of Neoplatonic metaphysics. Among these schemes is the target of each dialogue, whose relation to the theme can be explained, in a fruitful and innovative way, through a cosmic analogy. Thus (...) after examining the more or less explicit criticism of literary criteria of analysis by Plato's ancient exegetes, this article will focus on how Neoplatonists load the Greek termskopos(target) with metaphysical content and, accordingly, on how we should translate it in accordance with the commentators’ intentions. It will show that the target is the literary counterpart to the One, but that it should not be confused with the theme because the latter must be seen as the literary counterpart to the Intellect. (shrink)

Short (“seed”) or extended base pairing between microRNAs (miRNAs) and their target RNAs enables post‐transcriptional silencing in many organisms. These interactions allow the computational prediction of potential targets. In model organisms, predicted targets are frequently validated experimentally; hence meaningful miRNA‐regulated processes are reported. However, in non‐models, these reports mostly rely on computational prediction alone. Many times, further bioinformatic analyses such as Gene Ontology (GO) enrichment are based on these in silico projections. Here such approaches are reviewed, their caveats (...) are highlighted and the ease of picking false targets from predicted lists is demonstrated. Discoveries that shed new light on how miRNAs evolved to regulate targets in various phyletic groups are discussed, in addition to the pitfalls of target identification in non‐model organisms. The goal is to prevent the misuse of bioinformatic tools, as they cannot bypass the biological understanding of miRNA–target regulation. (shrink)

Much progress has been made in recent years regarding the mechanisms of targeting of secretory proteins to, and across, the endoplasmic reticulum (ER) membrane. Many of the cellular components involved in mediating translocation across this bilayer have been identified and characterized. Polypeptide domains of secretory proteins, termed signal peptides, have been shown to be necessary, and in most cases sufficient, for entry of preproteins into the lumen of the ER. These NH2‐ terminal segments appear to serve multiple roles in targeting (...) and translocation. The structural features which mediate their multiple functions are currently the subject of intense study. (shrink)

This paper by Prof. Daniel Statman, moral philosopher at the University of Haifa in Israel and author of the books Moral Dilemmas and Religion and Morality , offers a philosophical defense for such targeted killings or assassinations as those by Israel of Palestinians. The paper argues that if one accepts the moral legitimacy of the large-scale killing of combatants in conventional (what may come to be called 'old-fashioned') wars, one cannot object -- on moral grounds -- to the targeted killing (...) of terrorists in what are called wars against terror. If one rejects this legitimacy, one must object to all killing in war, targeted and non-targeted alike, and thus not support the view, which is criticized here, that targeted killings are particularly disturbing from a moral point of view. (shrink)

The question of how to contend with terrorism in keeping with our preexisting moral and legal commitments now challenges Europe as well as Israel and the United States: how do we apply Just War Theory and International Law to asymmetrical warfare, specifically to our counter terrorism measures? What can the classic moral argument in Just and Unjust Wars teach us about contemporary targeted killings with drones? I begin with a defense of targeted killing, arguing for the advantages of pin pointed (...) attacks over any alternative measure available for combatting terrorism. Assuming the legitimacy of killing combatants in wartime, I argue, there is nothing wrong, and in fact much that is right, with targeting particular terrorists selected by name, as long as their assassinations can be reasonably expected to reduce terrorist hostilities rather than increase it. Subsequently, I offer some further thoughts and comments on the use of remotely piloted aircrafts to carry out targeted killings, and address the various sources for discomfort with this practice identified by Michael Walzer and others. nema. (shrink)

Targeted killing is a subspecies of assassination, deployed against irregular combatants such as terrorists. The justification for targeted killing bypasses the usual ‘war paradigm’ and ‘criminal enforcement paradigm’, and is thus unusual. There are various ways of securing such a justification, but also a number of dangers attending these arguments.

We raise the following problem for so-called target-centred virtue ethics. An important motivation for adopting target-centred virtue ethics over other forms of virtue ethics is its supposedly distinctive account of right action: an action is right if and only if and because it is virtuous, and what makes an action virtuous is that it hits the target of the virtues. We argue that the account is not distinctive of target-centred virtue ethics, because it is an account that is widely endorsed (...) by Neo-Aristotelians. Hence, the argument of this paper undermines a central motivation for adopting target-centred virtue ethics. As a solution, we suggest that there is theoretical room for a target-centred account that is not Neo-Aristotelian, and we draw on the work of Confucian philosopher Wáng Yángmíng to provide one. We defend the resulting account by arguing that it has the advantage of being able to offer us a more plausible response to the self-centredness objection that has long been a problem for Neo-Aristotelians. (shrink)