Tailoring Targeted Therapy to Individual Patients: Lessons to be Learnt from the Development of Mitomycin C

The modern era of targeted therapeutics offers the potential to tailor therapy to individual patients whose tumours express a specific target. Previous attempts to forecast tumour response to conventional chemotherapeutics based on similar principles have however been disappointing. Mitomycin C (MMC), for example, is a bioreductive drug that requires metabolic activation by cellular reductases for activity. The enzyme NAD(P)H:Quinone oxidoreductase-1 (NQO1) can reduce MMC to DNA damaging species but attempts to establish the relationship between tumour response to MMC and NQO1 expression have generated conflicting reports of good and poor correlations. Several other reductases are known to activate MMC. This, in conjunction with the fact that various physiological and biochemical factors influence therapeutic response, suggests that the mechanism of action of MMC is too complex to allow tumour response to be predicted on the basis of a single enzyme. Alternative approaches using more complex biological and pharmacological systems that reflect the spectrum of reductases present within the tumour have been developed and it remains to be seen whether or not the predictive value of these approaches is enhanced. With regards to targeted therapeutics, the experience with MMC suggests that prediction of tumour response based on analysis of a single target may be too simplistic. Multiple mechanisms of action and the influence of tumour microenvironment on cell biology and drug delivery are likely to influence the final outcome of therapy. The challenge for the future progression of this field is to develop assays that reflect the overall biological and pharmacological processes involved in drug activation whilst retaining the simplicity and robustness required for routine chemosensitivity testing in a clinical setting

No more walls! A tale of modularity, symmetry, and wall crossing for 1/4 BPS dyons

Abstract We determine the generating functions of 1/4 BPS dyons in a class of 4d N $$\mathcal{N}$$ = 4 string vacua arising as CHL orbifolds of K3 × T 2, a classification of which has been recently completed. We show that all such generating functions obey some simple physical consistency conditions that are very often sufficient to fix them uniquely. The main constraint we impose is the absence of unphysical walls of marginal stability: discontinuities of 1/4 BPS degeneracies can only occur when 1/4 BPS dyons decay into pairs of 1/2 BPS states. Formally, these generating functions in spacetime can be described as multiplicative lifts of certain supersymmetric indices (twining genera) on the worldsheet of the corresponding nonlinear sigma model on K3. As a consequence, our procedure also leads to an explicit derivation of almost all of these twining genera. The worldsheet indices singled out in this way match precisely a set of functions of interest in moonshine, as predicted by a recent conjecture

Monstrous BPS-Algebras and the Superstring Origin of Moonshine

We provide a physics derivation of Monstrous moonshine. We show that the McKay-Thompson series $T_g$, $g\in \mathbb{M}$, can be interpreted as supersymmetric indices counting spacetime BPS-states in certain heterotic string models. The invariance groups of these series arise naturally as spacetime T-duality groups and their genus zero property descends from the behaviour of these heterotic models in suitable decompactification limits. We also show that the space of BPS-states forms a module for the Monstrous Lie algebras $\mathfrak{m}_g$, constructed by Borcherds and Carnahan. We argue that $\mathfrak{m}_g$ arise in the heterotic models as algebras of spontaneously broken gauge symmetries, whose generators are in exact correspondence with BPS-states. This gives $\mathfrak{m}_g$ an interpretation as a kind of BPS-algebra.Comment: 73 pages, with results summarized in introduction. v2: added a discussion about coupling to gravity (section 3.3), additional references, minor corrections and improvement

BPS Algebras, Genus Zero, and the Heterotic Monster

In this note, we expand on some technical issues raised in \cite{PPV} by the authors, as well as providing a friendly introduction to and summary of our previous work. We construct a set of heterotic string compactifications to 0+1 dimensions intimately related to the Monstrous moonshine module of Frenkel, Lepowsky, and Meurman (and orbifolds thereof). Using this model, we review our physical interpretation of the genus zero property of Monstrous moonshine. Furthermore, we show that the space of (second-quantized) BPS-states forms a module over the Monstrous Lie algebras $\mathfrak{m}_g$---some of the first and most prominent examples of Generalized Kac-Moody algebras---constructed by Borcherds and Carnahan. In particular, we clarify the structure of the module present in the second-quantized string theory. We also sketch a proof of our methods in the language of vertex operator algebras, for the interested mathematician.Comment: 19 pages, 2 figure

Heterotic sigma models on T8T^8 and the Borcherds automorphic form Φ12\Phi_{12}

We consider the spectrum of BPS states of the heterotic sigma model with $(0,8)$ supersymmetry and $T^8$ target, as well as its second-quantized counterpart. We show that the counting function for such states is intimately related to Borcherds' automorphic form $\Phi_{12}$, a modular form which exhibits automorphy for $O(2,26;{\mathbb Z})$. We comment on possible implications for Umbral moonshine and theories of AdS$_3$ gravity.Comment: 12 pages; v2 error (involving fermion zero modes) correcte

The Social Appearance Anxiety Scale in Italian adolescent populations: Construct validation and group discrimination in community and clinical eating disorders samples

Anxiety in situations where one’s overall appearance (including body shape) may be negatively evaluated is hypothesized to play a central role in Eating Disorders (EDs) and in their co-occurrence with Social Anxiety Disorder (SAD). Three studies were conducted among community (N = 1995) and clinical (N = 703) ED samples of 11- to 18-year-old Italian girls and boys to (a) evaluate the psychometric qualities and measurement equivalence/invariance (ME/I) of the Social Appearance Anxiety (SAA) Scale (SAAS) and (b) determine to what extent SAA or other situational domains of social anxiety related to EDs distinguish adolescents with an ED only from those with SAD. Results upheld the one-factor structure and ME/I of the SAAS across samples, gender, age categories, and diagnostic status (i.e., ED participants with and without comorbid SAD). The SAAS demonstrated high internal consistency and 3-week test–retest reliability. The strength of the inter-relationships between SAAS and measures of body image, teasing about appearance, ED symptoms, depression, social anxiety, avoidance, and distress, as well as the ability of SAAS to discriminate community adolescents with high and low levels of ED symptoms and community participants from ED participants provided construct validity evidence. Only SAA strongly differentiated adolescents with any ED from those with comorbid SAD (23.2 %). Latent mean comparisons across all study groups were performed and discussed

Compactified Strings as Quantum Statistical Partition Function on the Jacobian Torus

We show that the solitonic contribution of compactified strings correspond to the quantum statistical partition function of boson leaving on higher dimensional tori. In the simplest case of compactification in a circle, the Hamiltonian corresponds to the Laplacian on the 2g-dimensional Jacobian torus associated to the genus g Riemann surface corresponding to the string worldsheet. T-duality leads to a symmetry of the partition function mixing time and temperature. Such a classical/quantum correspondence and T-duality shed light on the well-known interplay between time and temperature in QFT and classical statistical mechanics