3,287 research outputs found
Law\u27s Territory (A History of Jurisdiction)
Pop quiz: New York City. The United Kingdom. The East Bay Area Municipal Utilities District. Kwazulu, South Africa. The Cathedral of Notre Dame. The State of California. Vatican City. Switzerland. The American Embassy in the U.S.S.R. What do the foregoing items have in common? Answer: they are, or were, all territorial jurisdictions. A thesis of this Article is that territorial jurisdictions - the rigidly mapped territories within which formally defined legal powers are exercised by formally organized governmental institutions - are relatively new and intuitively surprising technological developments. New, because until the development of modern cartography, legal authority generally followed relationships of status rather than those of autochthony. Today jurisdiction seems inevitable, but, like death, it is a habit to which consciousness has not been long accustomed. Surprising? We are now accustomed to territorial jurisdiction - so much so that it is hard to imagine that government could be organized any other way. But despite several hundred years of acclimation, people continue to be disoriented, baffled, and thrilled by the consequences of jurisdictional legality. We are filled with sometimes grudging admiration when the latest Esmeralda evades the territorial reach of the pursuing constable. Examples abound, both historical and fictional (or perhaps syncretic). Consider the trek of the musically gifted von Trapps to the safety of neutral Switzerland, the bootlegger\u27s run of Burt Reynolds\u27s Bandit who stopped just over the county line long enough to thumb his nose at Smokey Sheriff Buford T. Justice, the heroic and desperate journey on the fugitive slave\u27s underground railroad, the once heroic, now demonized, pregnant foreigner who struggles over the border in time to give birth on American soil and thereby guarantees her child American citizenship
Electrodynamics with radiation reaction
The self force of electrodynamics is derived from a scalar field. The
resulting equation of motion is free of all of the problems that plague the
Lorentz Abraham Dirac equation. The age-old problem of a particle in a constant
field is solved and the solution has intuitive appeal.Comment: 5 page
Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma
Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of the non-Hodgkin lymphomas and are currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options and short survival. The greatest challenge in improving survival of DLBCL patients is overcoming chemo-resistance, whose basis is poorly understood. Among the potential mediators of DLBCL chemo-resistance is the thioredxoin (Trx) family, primarily because Trx family members play critical roles in the regulation of cellular redox homeostasis, and recent studies have indicated that dysregulated redox homeostasis also plays a key role in chemoresistance. In this study, we showed that most of the DLBCL-derived cell lines and primary DLBCL cells express higher basal levels of Trx-1 than normal B cells and that Trx-1 expression level is associated with decreased patients survival. Our functional studies showed that inhibition of Trx-1 by small interfering RNA or a Trx-1 inhibitor (PX-12) inhibited DLBCL cell growth, clonogenicity, and also sensitized DLBCL cells to doxorubicin-induced cell growth inhibition in vitro. These results indicate that Trx-1 plays a key role in cell growth and survival, as well as chemoresistance, and is a potential target to overcome drug resistance in relapsed/refractory DLBCL
25 years of the WHO essential medicines lists: progress and challenges.
The first WHO essential drugs list, published in 1977, was described as a peaceful revolution in international public health. The list helped to establish the principle that some medicines were more useful than others and that essential medicines were often inaccessible to many populations. Since then, the essential medicines list (EML) has increased in size; defining an essential medicine has moved from an experience to an evidence-based process, including criteria such as public-health relevance, efficacy, safety, and cost-effectiveness. High priced medicines such as antiretrovirals are now included. Differences exist between the WHO model EML and national EMLs since countries face varying challenges relating to costs, drug effectiveness, morbidity patterns, and rationality of prescribing. Ensuring equitable access to and rational use of essential medicines has been promoted through WHO's revised drug strategy. This approach has required an engagement by WHO on issues such as the effect of international trade agreements on access to essential medicines and research and development to ensure availability of new essential medicines
ADHM Construction of Instantons on the Torus
We apply the ADHM instanton construction to SU(2) gauge theory on T^n x
R^(4-n)for n=1,2,3,4. To do this we regard instantons on T^n x R^(4-n) as
periodic (modulo gauge transformations) instantons on R^4. Since the R^4
topological charge of such instantons is infinite the ADHM algebra takes place
on an infinite dimensional linear space. The ADHM matrix M is related to a Weyl
operator (with a self-dual background) on the dual torus tilde T^n. We
construct the Weyl operator corresponding to the one-instantons on T^n x
R^(4-n). In order to derive the self-dual potential on T^n x R^(4-n) it is
necessary to solve a specific Weyl equation. This is a variant of the Nahm
transformation. In the case n=2 (i.e. T^2 x R^2) we essentially have an
Aharonov Bohm problem on tilde T^2. In the one-instanton sector we find that
the scale parameter, lambda, is bounded above, (lambda)^2 tv<4 pi, tv being the
volume of the dual torus tilde T^2.Comment: 35 pages, LATeX. New section on Nahm transform included, presentation
improved, reference added, to appear in Nuclear Physics
Adjustment of sensitisation and challenge protocols restores functional and inflammatory responses to ovalbumin in guinea-pigs
AbstractIntroductionInhalation of antigen in atopic asthma induces early (EAR) and late asthmatic responses (LARs), inflammatory cell infiltration and airways hyperresponsiveness (AHR). Previously, we have established a protocol of sensitisation and subsequent ovalbumin (Ova) inhalation challenge in guinea-pigs which induced these 4 features (Smith & Broadley, 2007). However, the responses of guinea-pigs to Ova challenge have recently declined, producing no LAR or AHR and diminished EAR and cells. By making cumulative modifications to the protocol, we sought to restore these features.MethodsGuinea-pigs were sensitised with Ova (i.p. 100 or 150μg) on days 1 and 5 or days 1, 4 and 7 and challenged with nebulised Ova (100 or 300μg/ml, 1h) on day 15. Airway function was measured in conscious guinea-pigs by whole-body plethysmography to record specific airway conductance (sGaw). Airway responsiveness to aerosolized histamine (0.3mM) was determined before and 24h after Ova challenge. Bronchoalveolar lavage was performed for total and differential inflammatory cell counts. Lung sections were stained for counting of eosinophils.ResultsLack of AHR and LAR with the original protocol was confirmed. Increasing the Ova challenge concentration from 100 to 300μg/ml restored AHR and eosinophils and increased the peak of the EAR. Increasing the number of sensitisation injections from 2 to 3 did not alter the responses. Increasing the Ova sensitisation concentration from 100 to 150μg significantly increased total cells, particularly eosinophils. A LAR was revealed and lymphocytes and eosinophils increased when either the Al(OH)3 concentration was increased or the duration between the final sensitisation injection and Ova challenge was extended from 15 to 21days.DiscussionThis study has shown that declining allergic responses to Ova in guinea-pigs could be restored by increasing the sensitisation and challenge conditions. It has also demonstrated an important dissociation between EAR, LAR, AHR and inflammation
Can we save large carnivores without losing large carnivore science?
Large carnivores are depicted to shape entire ecosystems through top-down processes. Studies describing these processes are often used to support interventionist wildlife management practices, including carnivore reintroduction or lethal control programs. Unfortunately, there is an increasing tendency to ignore, disregard or devalue fundamental principles of the scientific method when communicating the reliability of current evidence for the ecological roles that large carnivores may play, eroding public confidence in large carnivore science and scientists. Here, we discuss six interrelated issues that currently undermine the reliability of the available literature on the ecological roles of large carnivores: (1) the overall paucity of available data, (2) reliability of carnivore population sampling techniques, (3) general disregard for alternative hypotheses to top-down forcing, (4) lack of applied science studies, (5) frequent use of logical fallacies, and (6) generalisation of results from relatively pristine systems to those substantially altered by humans. We first describe how widespread these issues are, and given this, show, for example, that evidence for the roles of wolves (Canis lupus) and dingoes (Canis lupus dingo) in initiating trophic cascades is not as strong as is often claimed. Managers and policy makers should exercise caution when relying on this literature to inform wildlife management decisions. We emphasise the value of manipulative experiments, and discuss the role of scientific knowledge in the decision-making process. We hope that the issues we raise here prompt deeper consideration of actual evidence, leading towards an improvement in both the rigour and communication of large carnivore science
Large carnivore science: non-experimental studies are useful, but experiments are better
1. Response to Bruskotter and colleagues
We recently described the following six interrelated issues that justify questioning some of the discourse about the reliability of the literature on the ecological roles of large carnivores (Allen et al., in press):
1. The overall paucity of available data,
2. The reliability of carnivore population sampling techniques,
3. The general disregard for alternative hypotheses to top-down forcing,
4. The lack of applied science studies,
5. The frequent use of logical fallacies,
6. The generalisation of results from relatively pristine systems to those substantially altered by humans.
We thank Bruskotter et al. (2017) for responding to our concerns and engaging with this important issue. We agree completely that nonexperimental studies can and do often have great value, and we recognize that in many (most) cases these types of studies may provide the only data that are available. We acknowledge the many challenges of working on large, cryptic, dangerous, and highly-mobile animals in the wild. However, the absence of more robust data and the reality of these challenges do not excuse weak inference or overstating conclusions – a practice apparent in many studies (and communication of those studies) adopting only observational or correlative methods to infer the roles of large carnivores (reviewed in Allen et al., in press)
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