A
bstract
We construct the non-linear realisation of the semi-direct product of
E
11
and its first fundamental representation at lowest order and appropriate to spacetime dimensions four to seven. ...This leads to a non-linear realisation of the duality groups and introduces fields that depend on a generalised space which possess a generalised vielbein. We focus on the part of the generalised space on which the duality groups alone act and construct an invariant action.
Muscle Invasive bladder cancer is known to have an abundance of mutations, particularly in DNA damage response and chromatin modification genes. The role of these mutations in the development and ...progression of the disease is not well understood. However, a mutually exclusive mutation pattern between gene pairs could suggest gene mutations of significance. For example, a mutually exclusive mutation pattern could suggest an epistatic relationship where the outcome of a mutation in one gene would have the same outcome as a mutation in a different gene. The significance of a mutually exclusive relationship was determined by establishing a normal distribution of the conditional probabilities for having a mutation in one gene and not the other as well as the reverse relationship for each gene pairing. Then these distributions were used to determine the sigma-magnitude of standard deviation by which the observed value differed from the expected, a value that can also be interpreted as the 'p-value'. This approach led to the identification of mutually exclusive mutation patterns in KDM6A and KMT2D as well as KDM6A and RB1 that suggested the observed mutation pattern did not happen by chance. Upon further investigation of these genes and their interactions, a potential similar outcome was identified that supports the concept of epistasis. Knowledge of these mutational interactions provides a better understanding of the mechanisms underlying muscle invasive bladder cancer development, and may direct therapeutic development exploiting genotoxic chemotherapy and synthetic lethality in these pathways.
A
bstract
In the doubled field theory approach to string theory the T-duality group is promoted to a manifest symmetry at the expense of replacing ordinary Riemannian geometry with generalised ...geometry on a doubled space. The local symmetries are then given by a generalised Lie derivative and its associated algebra. This paper constructs an analogous structure for the extended geometry of M-theory. A crucial by-product of this construction is the derivation of the physical section condition for M-theory formulated in an extended space.
This study aimed to determine, in men recently diagnosed with grade group 1 (GG1) prostate cancer, if magnetic resonance imaging (MRI) with targeted biopsy could identify a greater proportion of men ...with GG ≥2 cancer on their confirmatory biopsy compared with systematic biopsies. The study was registered with www.clinicaltrials.gov (NCT01354171).
This study is a prospective, randomized, multicenter, open-label trial. Eligible patients were men diagnosed with GG1 cancer within 1 yr prior to study entry in whom a confirmatory biopsy was indicated. Patients were randomized to 12-core systematic biopsy or MRI with systematic and targeted biopsy using the Artemis fusion targeting system. The primary end point was the proportion upgraded to GG ≥2 in each arm.
In total, 296 men were registered and 273 randomized. Of the MRI group, 64% had a region of interest. No difference was observed in the rate of GG ≥2 upgrading (the intent-to-treat population, p=0.7, and per-protocol PP population, p=0.4), GG ≥2 upgrading within each stratum separately, or GG ≥3. After central pathology review, upgrading was observed in 36/132 (27%) men in the systematic biopsy arm and 42/127 (33%) men in the MRI arm (p=0.3). Upgrading was seen in 19/137 (14%) patients in the MRI arm on targeted biopsy alone (median, 2 cores) compared with 31/136 (23%) in the systematic biopsy arm (median, 12 cores; p=0.09). In the MRI arm, 8/127 (6.5%) patients had GG ≥2 disease identified on targeted biopsy, but ≤GG1 on the systematic biopsy, and 10/127 (7.9%) patients had GG ≥2 disease identified by systematic biopsy but ≤GG1 on targeted biopsy. Significant differences in upgrading on targeted biopsies were seen between sites, likely reflecting different levels of expertise with the targeted biopsy technique.
The addition of MRI with targeted biopsies to systematic biopsies did not significantly increase the upgrading rate compared with systematic biopsy alone. Furthermore, 2-core targeted biopsies alone resulted in a nonsignificant trend to less upgrading than 12-core systematic biopsy (p=0.09). In men on active surveillance, targeted biopsies identify most, but not all, clinically significant cancers.
This is the first report of a randomized, multicenter, prospective study in men on active surveillance for low-risk prostate cancer having their confirmatory biopsy. The study sought to compare the rate of upgrading to clinically significant cancer (Grade group ≥2), of systematic 12-core biopsy versus magnetic resonance imaging (MRI) with targeted biopsy. Systematic biopsies were also performed in the MRI group. The findings were that targeted biopsy using two cores per target in addition to systematic biopsies did not identify more significant cancers than systematic biopsies alone. Targeted biopsies identified the majority, but not all significant cancers compared with 12-core systematic biopsies. Systematic biopsies also missed some significant cancers. We conclude that, in men on active surveillance, targeted biopsies identify most, but not all, clinically significant cancers.
Global aspects of double geometry Berman, David S.; Cederwall, Martin; Perry, Malcolm J.
The journal of high energy physics,
09/2014, Letnik:
2014, Številka:
9
Journal Article
Recenzirano
Odprti dostop
A
bstract
We consider the concept of a generalised manifold in the
O
(
d, d
) setting, i.e., in double geometry. The conjecture by Hohm and Zwiebach for the form of finite generalised diffeomorphisms ...is shown to hold. Transition functions on overlaps are defined. Triple overlaps are trivial concerning their action on coordinates, but non-trivial on fields, including the generalised metric. A generalised manifold is an ordinary manifold, but the generalised metric on the manifold carries a gerbe structure. We show how the abelian behaviour of the gerbe is embedded in the non-abelian T-duality group. We also comment on possibilities and difficulties in the U-duality setting.
A
bstract
We consider the reduction of the duality invariant approach to M-theory by a U-duality group valued Scherk-Schwarz twist. The result is to produce potentials for gauged supergravities that ...are normally associated with non-geometric compactifications. The local symmetry reduces to gauge transformations with the gaugings exactly matching those of the embedding tensor approach to gauged supergravity. Importantly, this approach now includes a nontrivial dependence of the fields on the extra coordinates of the extended space.
Strings and branes are waves Berkeley, Joel; Berman, David S.; Rudolph, Felix J.
The journal of high energy physics,
06/2014, Letnik:
2014, Številka:
6
Journal Article
Recenzirano
Odprti dostop
A
bstract
We examine the equations of motion of double field theory and the duality manifest form of M-theory. We show the solutions of the equations of motion corresponding to null waves correspond ...to strings or membranes from the usual spacetime perspective. A Goldstone mode analysis of the null wave solution in double field theory produces the equations of motion of the duality manifest string.
We attempt to reformulate eleven dimensional supergravity in terms of an object that unifies the three-form and the metric and makes the M-theory duality group manifest. This short Letter deals with ...the case of where the U-duality group SO(5,5) acts in five spatial dimensions.
Cancer biomarker studies often require nucleic acid extraction from limited amounts of formalin-fixed, paraffin-embedded (FFPE) tissues, such as histologic sections or needle cores. A major challenge ...is low quantity and quality of extracted nucleic acids, which can limit our ability to perform genetic analyses, and have a significant influence on overall study design. This study was aimed at identifying the most reliable and reproducible method of obtaining sufficient high-quality nucleic acids from FFPE tissues. We compared the yield and quality of nucleic acids from 0.6-mm FFPE prostate tissue cores across 16 DNA and RNA extraction protocols, using 14 commercially available kits. Nucleic acid yield was determined by fluorometry, and quality was determined by spectrophotometry. All protocols yielded nucleic acids in quantities that are compatible with downstream molecular applications. However, the protocols varied widely in the quality of the extracted RNA and DNA. Four RNA and five DNA extraction protocols, including protocols from two kits for dual-extraction of RNA and DNA from the same tissue source, were prioritized for further quality assessment based on the yield and purity of their products. Specifically, their compatibility with downstream reactions was assessed using both NanoString nCounter gene expression assays and reverse-transcriptase real-time PCR for RNA, and methylation-specific PCR assays for DNA. The kit deemed most suitable for FFPE tissue was the AllPrep kit by Qiagen because of its yield, quality, and ability to purify both RNA and DNA from the same sample, which would be advantageous in biomarker studies.
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