On the π\pi and KK as qqˉq \bar q Bound States and Approximate Nambu-Goldstone Bosons

We reconsider the two different facets of $\pi$ and $K$ mesons as $q \bar q$ bound states and approximate Nambu-Goldstone bosons. We address several topics, including masses, mass splittings between $\pi$ and $\rho$ and between $K$ and $K^*$, meson wavefunctions, charge radii, and the $K-\pi$ wavefunction overlap.Comment: 15 pages, late

Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine

Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly solid tumours. This is due to a generally late-stage diagnosis of a primarily treatment-refractory disease. Several large-scale sequencing and mass spectrometry approaches have identified key drivers of this disease and in doing so highlighted the vast heterogeneity of lower frequency mutations that make clinical trials of targeted agents in unselected patients increasingly futile. There is a clear need for improved biomarkers to guide effective targeted therapies, with biomarker-driven clinical trials for personalised medicine becoming increasingly common in several cancers. Interestingly, many of the aberrant signalling pathways in PDAC rely on downstream signal transduction through the mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K) pathways, which has led to the development of several approaches to target these key regulators, primarily as combination therapies. The following review discusses the trend of PDAC therapy towards molecular subtyping for biomarker-driven personalised therapies, highlighting the key pathways under investigation and their relationship to the PI3K pathway

The synthesis, conformation and hydrolytic stability of an N,S-bridging thiophosphoramidate analogue of thymidylyl-3 ',5 '-thymidine

A 3 ’ - N ,5 ’ - S -bridging thiophosphoramidate analogue of thymidylyl-3 ’ ,5 ’ -thymidine was synthesised underaqueous conditions.1H NMR conformational measurements show that the 3 ’ - N -substituted deoxyribosering is biased towards the ‘ north ’ , RNA-like conformation. Rate constants for hydrolysis of the analoguewere measured at 90 °C in the pH range 1.3 – 10.9. The pH-log k obs pro fi le displays a pH-independentregion between approximately pH 7 and 10 ( t 1/2 ∼ 13 days). Under acidic conditions, k obs displays a fi rstorder dependence on [H 3 O+]</p

Finding Shuffle Words That Represent Optimal Scheduling of Shared Memory Access

In the present paper, we introduce and study the problem of computing, for any given finite set of words, a shuffle word with a minimum so-called scope coincidence degree. The scope coincidence degree is the maximum number of different symbols that parenthesise any position in the shuffle word. This problem is motivated by an application of a new automaton model and can be regarded as the problem of scheduling shared memory accesses of some parallel processes in a way that minimises the number of memory cells required. We investigate the complexity of this problem and show that it can be solved in polynomial time

Parity proofs of the Bell-Kochen-Specker theorem based on the 600-cell

The set of 60 real rays in four dimensions derived from the vertices of a 600-cell is shown to possess numerous subsets of rays and bases that provide basis-critical parity proofs of the Bell-Kochen-Specker (BKS) theorem (a basis-critical proof is one that fails if even a single basis is deleted from it). The proofs vary considerably in size, with the smallest having 26 rays and 13 bases and the largest 60 rays and 41 bases. There are at least 90 basic types of proofs, with each coming in a number of geometrically distinct varieties. The replicas of all the proofs under the symmetries of the 600-cell yield a total of almost a hundred million parity proofs of the BKS theorem. The proofs are all very transparent and take no more than simple counting to verify. A few of the proofs are exhibited, both in tabular form as well as in the form of MMP hypergraphs that assist in their visualization. A survey of the proofs is given, simple procedures for generating some of them are described and their applications are discussed. It is shown that all four-dimensional parity proofs of the BKS theorem can be turned into experimental disproofs of noncontextuality.Comment: 19 pages, 11 tables, 3 figures. Email address of first author has been corrected. Ref.[5] has been corrected, as has an error in Fig.3. Formatting error in Sec.4 has been corrected and the placement of tables and figures has been improved. A new paragraph has been added to Sec.4 and another new paragraph to the end of the Appendi

Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology.

Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to better inform lead compound development and address the increasing attrition rates of lead compounds within the pharmaceutical industry, which are often a result of screening in less faithful two-dimensional models. Using large-scale acid-extraction techniques, we demonstrate a step-by-step process to isolate collagen I from commercially available animal byproducts. Using the well-established rat tail tendon collagen as a benchmark, we apply our novel kangaroo tail tendon collagen as an alternative collagen source for our screening-ready three-dimensional organotypic co-culture platform. Both collagen sources showed equal applicability for invasive, proliferative or survival assessment of well-established cancer models and clinically relevant patient-derived cancer cell lines. Additional readouts were also demonstrated when comparing these alternative collagen sources for stromal contributions to stiffness, organization and ultrastructure via atomic force microscopy, second harmonic generation imaging and scanning electron microscopy, among other vital biological readouts, where only minor differences were found between the preparations. Organotypic co-cultures represent an easy, affordable and scalable model to investigate drug responses within a physiologically relevant 3D platform

Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease- and drug-dependent dynamic regulation of cell-cell junctions in live tissue

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments

Kac-Moody algebras in perturbative string theory

The conjecture that M-theory has the rank eleven Kac-Moody symmetry e11 implies that Type IIA and Type IIB string theories in ten dimensions possess certain infinite dimensional perturbative symmetry algebras that we determine. This prediction is compared with the symmetry algebras that can be constructed in perturbative string theory, using the closed string analogues of the DDF operators. Within the limitations of this construction close agreement is found. We also perform the analogous analysis for the case of the closed bosonic string.Comment: 31 pages, harvmac (b), 4 eps-figure