859 research outputs found
Gr\"obner Bases and Nullstellens\"atze for Graph-Coloring Ideals
We revisit a well-known family of polynomial ideals encoding the problem of
graph--colorability. Our paper describes how the inherent combinatorial
structure of the ideals implies several interesting algebraic properties.
Specifically, we provide lower bounds on the difficulty of computing Gr\"obner
bases and Nullstellensatz certificates for the coloring ideals of general
graphs. For chordal graphs, however, we explicitly describe a Gr\"obner basis
for the coloring ideal, and provide a polynomial-time algorithm.Comment: 16 page
Evaluating diagnostic strategies for early detection of cancer: the CanTest framework
Abstract: Background: Novel diagnostic triage and testing strategies to support early detection of cancer could improve clinical outcomes. Most apparently promising diagnostic tests ultimately fail because of inadequate performance in real-world, low prevalence populations such as primary care or general community populations. They should therefore be systematically evaluated before implementation to determine whether they lead to earlier detection, are cost-effective, and improve patient safety and quality of care, while minimising over-investigation and over-diagnosis. Methods: We performed a systematic scoping review of frameworks for the evaluation of tests and diagnostic approaches. Results: We identified 16 frameworks: none addressed the entire continuum from test development to impact on diagnosis and patient outcomes in the intended population, nor the way in which tests may be used for triage purposes as part of a wider diagnostic strategy. Informed by these findings, we developed a new framework, the ‘CanTest Framework’, which proposes five iterative research phases forming a clear translational pathway from new test development to health system implementation and evaluation. Conclusion: This framework is suitable for testing in low prevalence populations, where tests are often applied for triage testing and incorporated into a wider diagnostic strategy. It has relevance for a wide range of stakeholders including patients, policymakers, purchasers, healthcare providers and industry
Human peroxisomal coenzyme A diphosphatase (NUDT7): a target enabling package (TEP)
In an effort to characterise the human NUDIX family SGC Oxford has expressed recombinant human NUDT7 as part of the SGC chemical probe programme and solved the first crystal structure of this enzyme. This enabled a crystallographic fragment screen which in conjunction with a separate covalent fragment approach yielded a first-in-class small molecule inhibitor of NUDT7 with activity in the single-digit micromolar range in a catalytic assay. This compound paves the way for chemical probe development and further functional exploration of NUDT7 in physiological and disease contexts
The Cosmic Origins Spectrograph
The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F(sub lambda) approximates 1.0 X 10(exp -14) ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011. COS has measured, for the first time with high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium, and observed the HeII reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-beta-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential beta-lactamase stable beta-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.Peer reviewe
The Cosmic Origins Spectrograph
The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph
with unprecedented sensitivity that was installed into the Hubble Space
Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We
present the design philosophy and summarize the key characteristics of the
instrument that will be of interest to potential observers. For faint targets,
with flux F_lambda ~ 1.0E10-14 ergs/s/cm2/Angstrom, COS can achieve comparable
signal to noise (when compared to STIS echelle modes) in 1-2% of the observing
time. This has led to a significant increase in the total data volume and data
quality available to the community. For example, in the first 20 months of
science operation (September 2009 - June 2011) the cumulative redshift
pathlength of extragalactic sight lines sampled by COS is 9 times that sampled
at moderate resolution in 19 previous years of Hubble observations. COS
programs have observed 214 distinct lines of sight suitable for study of the
intergalactic medium as of June 2011. COS has measured, for the first time with
high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium,
and observed the HeII reionization epoch along multiple sightlines. COS has
detected the first CO emission and absorption in the UV spectra of low-mass
circumstellar disks at the epoch of giant planet formation, and detected
multiple ionization states of metals in extra-solar planetary atmospheres. In
the coming years, COS will continue its census of intergalactic gas, probe
galactic and cosmic structure, and explore physics in our solar system and
Galaxy.Comment: 17 pages, 15 figure
International Nonregimes: A Research Agenda1
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146934/1/j.1468-2486.2007.00672.x.pd
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