Marginal Cases Research Articles

ROTATIONAL SYNCHRONIZATION MAY ENHANCE HABITABILITY FOR CIRCUMBINARY PLANETS: KEPLER BINARY CASE STUDIES

We report a mechanism capable of reducing (or increasing) stellar activity in binary stars, thereby potentially enhancing (or destroying) circumbinary habitability. In single stars, stellar aggression towards planetary atmospheres causes mass-loss, which is especially detrimental for late-type stars, because habitable zones are very close and activity is long lasting. In binaries, tidal rotational breaking reduces magnetic activity, thus reducing harmful levels of XUV radiation and stellar mass-loss that are able to erode planetary atmospheres. We study this mechanism for all confirmed circumbinary (p-type) planets. We find that main sequence twins provide minimal flux variation and in some cases improved environments, if the stars rotationally synchronize within the first Gyr. Solar-like twins, like Kepler 34 and Kepler 35, provide low habitable zone XUV fluxes and stellar wind pressures. These wide, moist, habitable zones may potentially support multiple habitable planets. Solar-type stars with lower mass companions, like Kepler 47, allow for protected planets over a wide range of secondary masses and binary periods. Kepler 38 and related binaries are marginal cases. Kepler 64 and analogues have dramatically reduced stellar aggression due to synchronization of the primary, but are limited by the short lifetime. Kepler 16 appears to be inhospitable to planets due to extreme XUV flux. These results have important implications for estimates of the number of stellar systems containing habitable planets in the Galaxy and allow for the selection of binaries suitable for follow-up searches for habitable planets.

Extracorporeal Hepatic Resection and Autotransplantation Using Temporary Portocaval Shunt Provides an Improved Solution for Conventionally Unresectable HCC

Hepatic resection is the gold-standard treatment for hepatocellular carcinoma (HCC). In East Asia, however, only 20 % of patients with HCC are eligible for hepatectomy [1]. In a small subset of patients, surgical resection using conventional techniques is extremely challenging. In these marginal cases, the tumor size, extension of the lesion, and proximity of the tumor to critical structures are important factors determining how to proceed. For tumors considered unresectable by conventional means, extracorporeal hepatic resection with autotransplantation (ECHRA) has been proposed to be an alternative [2]. ECHRA has been used to treat hepatic pathologies including giant hemangioma [3], liver metastases [4], and sarcomas [2]. However, few studies have reported on its application as a treatment for HCC [5]. Herein we report a case series involving three consecutive patients with HCC who were successfully treated with ECHRA as curative therapy for otherwise unresectable HCCs.

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT–PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.

MicroRNAs as prognostic markers in indolent primary cutaneous B-cell lymphoma

Indolent primary cutaneous B-cell lymphoma is a group of malignant lymphomas comprising marginal zone B-cell lymphoma and centrofollicular B-cell lymphoma. Relapse rate of these tumors is close to 40%, and identifying those patients who are likely to progress remains a challenge. The aim of this study was to characterize the microRNA (miRNA) expression profile of a series of primary cutaneous B-cell lymphomas and correlate with histological and clinical findings. We studied a series of 68 patients with primary cutaneous B-cell lymphomas (30 cutaneous marginal-zone B-cell lymphomas and 38 primary cutaneous centrofollicular lymphomas). A set of 11 miRNAs associated with the differentiation stage of B cells was quantified by real-time PCR, using RNA extracted from formalin-fixed, paraffin-embedded tissue diagnostic samples. Relevant clinical variables were retrieved in a subset of 57 patients (28 cutaneous marginal zone B-cell lymphomas and 29 primary cutaneous centrofollicular lymphomas). miR-150 was upregulated in cutaneous marginal zone B-cell lymphomas relative to primary cutaneous centrofollicular lymphoma samples (false discovery rate <0.05). miR-155 and miR-150 expression levels were associated with progression-free survival in a univariate Cox regression analysis (P<0.1). After stratification by histological subtype, low-expression levels of miR-155 and miR-150 were both associated with shorter progression-free survival only in primary cutaneous marginal zone B-cell lymphomas cases (log-rank test, P<0.05). In summary, miRNA expression analysis can be used as a tool for diagnosis and outcome prognosis in indolent primary cutaneous B-cell lymphoma.

QUALITIES OF WILL

AbstractOne of P. F. Strawson's suggestions in “Freedom and Resentment” was that there might be an elegant theory of moral responsibility that accounted for all of our responsibility responses (our “reactive attitudes,” in his words) in a way that also explained why we get off the hook from those responses. Such a theory would appeal exclusively toquality of will: when we react with any of a variety of responsibility responses to someone, we are responding to the quality of her will with respect to us, and when we let her off the hook (either for her action or with respect to her qua agent), we are doing so in virtue of her lacking the capacity for the relevant quality of will. Strawson's own attempt to put forward such a view fails, for reasons Gary Watson has given, but several other theorists have advanced their own, more developed,Pure Quality of Willtheories in recent years (including Scanlon, Arpaly, and McKenna). Specifically, there have been three distinct interpretations of “will” defended in the literature, yielding three different possible targets of our responsibility responses: quality ofcharacter, quality ofjudgment, or quality ofregard.My first task in this essay will be to show that none of these theories individually can captureallof our responsibility responses, given our deeply ambivalent responses to several marginal cases (e.g., psychopathy, clinical depression, Alzheimer's dementia). One reaction to this fact might be to abandon the quality of will approach altogether. Another, more plausible, reaction is to develop a pluralistic account of responsibility, one that admits three noncompeting conceptions of responsibility, each of which emphasizes one of the three different qualities of will as the target of a distinct subset of our responsibility responses. On this pluralistic approach, marginal agents might be responsible on some conceptions, but not responsible on others. In the bulk of the paper, I discuss each of the relevant subsets of responsibility responses, the different qualities of will they target, what the capacities for the three qualities of will are, and how the pluralistic qualities of will approach could account for our ambivalence in the marginal cases.

‘Pass the Cocoamone, Please’: Causal Impotence, Opportunistic Vegetarianism and Act-Utilitarianism

It appears that utilitarian arguments in favor of moral vegetarianism cannot justify a complete prohibition of eating meat. This is because, in certain circumstances, forgoing meat will prevent no pain, and so, on utilitarian grounds, we should be opportunistic carnivores rather than moral vegetarians. In his paper, ‘Puppies, pigs, and people: Eating meat and marginal cases,’ Alastair Norcross argues that causal impotence arguments like these are misguided. First, he presents an analogous situation, the case of chocolate mousse a-la-bama, in order to argue that we, individually, are not causally impotent. Second, Norcross offers a threshold argument in which he argues that while we may individually be causally impotent, when we adopt moral vegetarianism in concert with others, we become causally potent in preventing harms by factory farming. We argue that Norcross's responses ultimately fail to address the causal impotence objection. The former argument fails because it vastly oversimplifies the world in which we find ourselves. Given the size of factory farming, the reasonable conclusion is that we are in fact powerless to prevent harms to animals in factory farms in many or most cases. The latter argument fails because even if collective action will have an impact on factory farming, this does not provide us with an argument against being carnivores in certain circumstances.

Elucidating the Role of Dose in the Biopharmaceutics Classification of Drugs: The Concepts of Critical Dose, Effective In Vivo Solubility, and Dose-Dependent BCS

To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose. We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose for the various classes of BCS and the marginal cases in between classes. Simulations based on the mathematical model of F versus dose produced patterns of a constant F throughout a wide range of doses for drugs of Classes I, II and III, justifying biowaiver claim. For Classes I and III the pattern of a constant F stops at a critical dose Dose(cr) after which the amount of drug absorbed, is independent from the dose. For doses higher than Dose(cr), Class I drugs become Class II and Class III drugs become Class IV. Dose(cr) was used to define an in vivo effective solubility as S(eff) = Dose(cr)/250 ml. Literature data were used to support our simulation results. A new biopharmaceutic classification of drugs is proposed, based on F, separating drugs into three regions, taking into account the dose, and Dose(cr), while the regions for claiming biowaiver are clearly defined.

An analytical model for the performance evaluation of multistage interconnection networks with two class priorities

The aim of this paper is to develop an analytical method for performance evaluation of double prioritized Multistage Interconnected Networks (MINs) with single or multilayers and backpressure operation which provide service differentiation and QoS guarantee to an end application running over next generation Internet or Grid systems. Specifically, a new architecture of switching elements is used for the construction of MINs. This switch element uses two parallel queues in order to serve dual priority traffic. Besides this, uniform traffic conditions are presupposed and the bulk of packet arrivals in each cycle to the network inputs follow a Bernoulli distribution. A new analytical model for evaluating single buffered MIN’s with 2×2 special switching elements supporting internally two classes’ priority traffic is presented. Equations for the steady state are derived. These equations are then used in finding the most important multistage network performance metrics, such as throughput, and packet latency. The results are also validated using simulation and compared with previous related work in marginal cases. This proposed analytical model is accurate for various network sizes and various values of offered traffic to the multistage network inputs.

Legal Realism Untamed

What makes hard cases hard, and what makes easy cases easy? A common response to H.L.A. Hart’s (mis)reading of Legal Realist is that the Realists offered their arguments solely in the context of the hard or indeterminate cases likely to find their way into appellate courts. Llewellyn, for example, made clear that his claims were restricted to “any case doubtful enough to make litigation respectable,” and Max Radin limited his Realist claims to “marginal cases.” Thus, a “tamed” version of Realism limits the Realists’ claims to the self-selected but non-representative group of disputes that are the stuff of reported appellate decisions. And this version is “tamed” because it is compatible with the view that standard legal sources determine the outcome in the cases that are not doubtful and would be futile to litigate. Indeed, the version is so tamed that it is largely compatible with Hart’s own response to the Realists. But although many commentators, including this author, have at times subscribed to this effort to tame Realism, that effort may understate the magnitude of the Realist challenge by understating the effect of the gap between paper rules and real rules, to use Llewellyn’s terminology, on the makeup of the array of cases that are or are not doubtful. If, as Llewellyn and others argued, factors other than the standard (or literal) reading of standard legal sources determine the outcome even when the standard legal sources are clear, then the existence of such non-standard sources will make cases that are not doubtful under the traditional picture doubtful – and thus worth litigating. And if this is so, then the divergence between real rule and paper rule will be relevant not only in doubtful cases, but also in determining which cases are doubtful and which not. Realism would then be a claim not merely about doubtful cases, but a claim pervading the entire operation of a system of legal rules. To the extent that the claim is true, therefore, it represents a serious attack on the traditional picture of law throughout its operation, and not simply in the doubtful cases. To the extent that easy cases are easy not because of the plain meaning of the language of a written-down or black-letter legal rule, and thus to the extent that hard cases are hard not because of the indeterminacy of the language of such rules, the entire array of cases selected for litigation, and deselected from litigation, will be determined by factors not to be found in the paper rules. In this sense, American Legal Realism constitutes a less bounded -- and thus untamed -- attack on the traditional picture of law, although the ultimate soundness of the challenge still depends on empirical facts about the relationship, if any, between the paper rules and the real rules.

Measurement Issues: Screening and diagnostic instruments for autism spectrum disorders - lessons from research and practise.

Significant progress has been made over the past two decades in the development of screening and diagnostic instruments for autism spectrum disorders (ASDs). This article reviews this progress, including recent innovations, focussing on those instruments for which the strongest research data on validity exists, and then addresses issues arising from their use in clinical settings. Research studies have evaluated the ability of screens to prospectively identify cases of ASD in population-based and clinically referred samples, as well as the accuracy of diagnostic instruments to map onto 'gold standard' clinical best estimate diagnosis. However, extension of the findings to clinical services must be done with caution, with a full understanding that instrument properties are sample-specific. Furthermore, we are limited by the lack of a true test for ASD which remains a behaviourally defined disorder. In addition, screening and diagnostic instruments help clinicians least in the cases where they are most in want of direction, as their accuracy will always be lower for marginal cases. Instruments help clinicians to collect detailed, structured information and increase accuracy and reliability of referral for in-depth assessment and recommendations for support, but further research is needed to refine their effective use in clinical settings.

Method of Light Bulbs Analysis on Vehicles Damaged in Traffic Accidents

One of the measures to increase road traffic safety in Croatia is the introduction of obligatory use of daily lights on vehicles in road traffic during driving, regardless of the visibility and the time of day. The paper describes the new original technical and technological procedure of analysing automotive light bulbs in order to find the traces of glass particles of the broken glass balloon in the marginal cases of action of small inertia forces generated as result of a traffic accident. Investigations of light bulbs in traffic accidents had been rarely done before; therefore the subject of this scientific research is the analysis of the light bulb filament used in automobiles to light the road ahead and to give light signals, i.e. all the light signalling devices on the automobile using the new technical and technological procedure by means of SEM/EDX method. The scientific research has improved the investigation procedure in analysing the light bulbs on automobiles in determining whether at the moment of the traffic accident the regulatory lights were switched on. In determining the responsibility of participants for causing the traffic accident, such a fact may sometimes be of crucial significance. KEY WORDS: traffic accident, light bulb, technical and technological procedure, lights in traffic, microscope, molten glass particles

On Defining Music

Music is ancient, pancultural, and, given the spontaneous emergence of song in children, virtually universal. Moreover, we can immediately and recognize it, even where it comes from a culture that is foreign to us. Though I may be unable to predict how such will continue or to recognize errors, and though it may sound strange to me, I can be in no doubt that it is I am hearing.I say almost infallibly because there are marginal cases and a few possibilities for error. Some musical-sounding things are not music: infantdirected speech,1 tone languages,2 and sing-song linguistic accents, as in Welsh. In addition, some patterned might be mistaken for music: these include sound art,3 that are not humanly made, such as the nightly rice field frog chorus, and that are not primarily intended to have the aural character they have, such as incidental auditory effects in the factory making crystal glasses.In this paper I reflect on the enterprise of defining music. Although I critically review some proposed definitions in order to show the difficulties inherent in the task, I do not offer a counterdefinition. Instead, I consider four strategies that might be adopted by the would-be definer. I argue that none of these alone can succeed, though, in combination, they might.1. Some Definitions of MusicCompared to art, philosophers have not shown much interest in defining music. In fact, definitions of are rarely attempted. I am not sure why this is the case. Perhaps it is because, as was observed earlier, we are usually highly successful in identifying as such, and don't feel the need of a definition. And the task of producing a watertight definition of such a wide-ranging phenomenon as is not only thankless but also challenging. To indicate the obstacles that stand in the way and to consider strategies for negotiating them, I now briefly discuss proposals advanced by Jerrold Levinson and Andrew Kania.Levinson, whose goal is to define as an art, proposes that is temporally organized by a person for the purpose of enriching or intensifying experience through active engagement (e.g., listening, dancing, performing) with the regarded primarily, or in significant measure, as sounds (1990, 273). He is happy to exclude Muzak on the grounds that it is not intended for attention and birdsong because it is not humanly created or artistically motivated, though he allows birdsong to qualify under a secondary, legitimate use of music where it refers simply to a type of sonic phenomenon, namely one that musical. He concedes John Cage's silent piece 4 '33 as a limiting case of music, since Cage has organized for listening the anticipated but unpredictable that will occur during a (1990, 270, fh. 3). He denies, however, that this shows that any sounds, when not so framed, are music. At most it shows that any can be treated as i/they are music.Perhaps unsurprisingly, philosophers disagree about the status of Cage's 4 '33 , so before evaluating Levinson 's definition I sketch my view of the piece. Though I have not provided a definition, I have argued (Davies 2003) that if is organized sound, however liberally we construe the notion of organization, it must be the case that some are excluded such that, were they to occur during a performance, they would be ambient to it. Cage's work is usually understood as absorbing all the that take place in the performance period as its contents, so that none count as ambient. In that case, Cage's piece fails the necessary condition for that I have proposed. I conclude that, as an artwork, 4 '33 is a performance piece, a theatrical work if you will, about the performance of music, not a musical work as such.The main difficulty with Levinson's definition, I think, is that does not and is not always intended to call attention to itself. …

Cosmic censorship in overcharging a Reissner-Nordström black hole via charged particle absorption

There is a claim that a static charged black hole (Reissner-Nordstr\"{o}m black hole) can be overcharged by absorbing a charged test particle. If it is true, it might give a counter example to the weak cosmic censorship conjecture, which states that spacetime singularities are never observed by a distant observer. However, so far the proposed process has only been analyzed within a test particle approximation. Here we claim that the back reaction effects of a charged particle cannot be neglected when judging whether the suggested process is really a counter example to the cosmic censorship conjecture or not. Furthermore, we argue that all the back reaction effects can be properly taken into account when we consider the trajectory of a particle on the border between the plunge and bounce orbits. In such marginal cases we find that the Reissner-Nordstr\"{o}m black hole can never be overcharged via the absorption of a charged particle. Since all the plunge orbits are expected to have a higher energy than the marginal orbit, we conclude that there is no supporting evidence that indicates the violation of the cosmic censorship in the proposed overcharging process.

Collocation, interpretation and explanation: The case of just any

This article discusses the question of compositionality by examining whether the indiscriminacy reading of the collocation of just with any can be shown to be a consequence of the schematic meaning-potential of each of these two items. A comparison of just with other restrictive focus particles allows its schematic meaning to be defined as that of goodness of fit. Any is defined as representing an indefinite member of a set as extractable from the set in exactly the same way as each of the other members thereof. The collocation just any often gives rise to a scalar reading oriented towards the lowest value on the scale due to the fact that focus on the unconstrained extractability of a random indefinite item brings into consideration even marginal cases and the latter tend to be interpreted as situated on the lower end of the scale. The attention to low-end values also explains why just any is regularly found with the adjective old, the prepositional phrase at all and various devaluating expressions. It is concluded that the meanings of the component parts of this collocation do indeed account for the meaning of the whole, and that an appropriate methodology allows identification of linguistic meanings and their interrelations.

PIM2 inhibition as a rational therapeutic approach in B-cell lymphoma

AbstractPIM serine/threonine kinases are overexpressed, translocated, or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma, diffuse large B-cell lymphoma (DLBLC), follicular lymphoma, marginal zone lymphoma-mucosa–associated lymphoid tissue type, chronic lymphocytic leukemia, and nodal marginal zone lymphoma cases. Increased PIM2 protein expression was associated with an aggressive clinical course in activated B-like-DLBCL patients. Pharmacologic and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity and indicated the involvement of PIM2 kinase in regulating mammalian target of rapamycin complex 1. The simultaneous genetic inhibition of all 3 PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification.

A Response to Deckers

Abstract In this short article I respond, both positively and negatively, but mostly positively, to Jan Deckers’ examination of my defense of nonhuman animal rights from the perspective of process philosophy and from the perspective of what is commonly called the argument from marginal cases.

Analytical model for performance-evaluation of multistage interconnection networks supporting multi-class priority service

In this paper, a discrete-time, single server with parallel multi-buffers, switching element (SE) is presented and analysed. This SE is used in the construction of multistage interconnection networks which have the ability to service the multi-priority traffic-supporting good quality of service. Through a queuing analysis and under various values of multi-traffic classifications, a performance evaluation is determined. This analytical model is based on the steady-state description of the system behaviour. An utilisation's formula is extracted by considering the steady state of the discrete-time multistage network. Consequently, we estimated the rest of the performance metrics. The results are validated using simulation. Apart from that our multi-priority architecture, validated in marginal cases, is compared to some existing single and two class priority models of multistage networks. This comparison is made by gathering metrics and comparing the total packet throughput. Also, the gain of the high-priority packets against the lower-priority packets under different configuration schemas is demonstrated. Eventually, this proposed analytical model is very accurate for various network sizes, with various values of offered multi-priority traffic on fabric's inputs and, therefore, can be used in performance prediction of multistage networks which supports quality of service.

A HÖLDER–YOUNG–LIEB INEQUALITY FOR NORMS OF GAUSSIAN WICK PRODUCTS

An important connection between the finite-dimensional Gaussian Wick products and Lebesgue convolution products will be proven first. Then this connection will be used to prove an important Hölder inequality for the norms of Gaussian Wick products, reprove Nelson hypercontractivity inequality, and prove a more general inequality whose marginal cases are the Hölder and Nelson inequalities mentioned before. We will show that there is a deep connection between the Gaussian Hölder inequality and classic Hölder inequality, between the Nelson hypercontractivity and classic Young inequality with the sharp constant, and between the third more general inequality and an extension by Lieb of the Young inequality with the best constant. Since the Gaussian probability measure exists even in the infinite-dimensional case, the above three inequalities can be extended, via a classic Fatou's lemma argument, to the infinite-dimensional framework.

A predictive model based on tortuosity for pressure drop estimation in ‘ slim’ and ‘ fat’ foams

The use of porous structures with high external surface area represents an important breakthrough in several industrial applications. Foam structures have received an increasing scientific and industrial interest since the last decade. Knowledge of pressure drop induced by these foam structures is thus essential for successful design and operation of high performance industrial systems. In this context, an analytical investigation was conducted for the determination of the permeability and the inertial coefficient in foams. The theoretical model is based on modified cubic lattice, which allows to take into account the presence of matter at the junction of struts. The existing model developed in the literature is then modified to incorporate this geometrical approach for determining the tortuosity of the foam. Finally, the permeability and inertial coefficient analysis are performed in order to derive the pressure drop on foams. The modeling procedure is based only on physical principles and geometrical considerations with no adjustable parameters in order to reconcile the theoretical work with the experimental data of the literature. Finally, this model is validated for two marginal cases (i.e. ‘ slim’ and ‘ fat’ foams).

Causal effects of foster care: An instrumental-variables approach

Abstract This paper describes the use of instrumental-variables (IV) to estimate causal effects of foster care on long- and short-term outcomes. This estimation strategy provides a tool to evaluate what are known as “natural experiments”: settings that mimic randomization usually associated with a controlled trial. The proposed natural experiment involves the effective randomization of investigators to child-protection cases. The results suggest that foster care placement increases like likelihood of delinquency and emergency healthcare episodes. Care must be taken when interpreting IV estimates. The results apply to cases that are part of the natural experiment—“marginal cases” where the investigators may disagree about the placement recommendation.