Encoding of Marginal Utility across Time in the Human Brain

Marginal utility theory prescribes the relationship between the objective property of the magnitude of rewards and their subjective value. Despite its pervasive influence, however, there is remarkably little direct empirical evidence for such a theory of value, let alone of its neurobiological basis. We show that human preferences in an intertemporal choice task are best described by a model that integrates marginally diminishing utility with temporal discounting. Using functional magnetic resonance imaging, we show that activity in the dorsal striatum encodes both the marginal utility of rewards, over and above that which can be described by their magnitude alone, and the discounting associated with increasing time. In addition, our data show that dorsal striatum may be involved in integrating subjective valuation systems inherent to time and magnitude, thereby providing an overall metric of value used to guide choice behavior. Furthermore, during choice, we show that anterior cingulate activity correlates with the degree of difficulty associated with dissonance between value and time. Our data support an integrative architecture for decision making, revealing the neural representation of distinct subcomponents of value that may contribute to impulsivity and decisiveness

Wavefunctions and the Point of E8 in F-theory

In F-theory GUTs interactions between fields are typically localised at points of enhanced symmetry in the internal dimensions implying that the coefficient of the associated operator can be studied using a local wavefunctions overlap calculation. Some F-theory SU(5) GUT theories may exhibit a maximum symmetry enhancement at a point to E8, and in this case all the operators of the theory can be associated to the same point. We take initial steps towards the study of operators in such theories. We calculate wavefunctions and their overlaps around a general point of enhancement and establish constraints on the local form of the fluxes. We then apply the general results to a simple model at a point of E8 enhancement and calculate some example operators such as Yukawa couplings and dimension-five couplings that can lead to proton decay.Comment: 46 page

The value of what’s to come: Neural mechanisms coupling prediction error and the utility of anticipation

Having something to look forward to is a keystone of well-being. Anticipation of future reward, such as an upcoming vacation, can often be more gratifying than the experience itself. Theories suggest the utility of anticipation underpins various behaviors, ranging from beneficial information-seeking to harmful addiction. However, how neural systems compute anticipatory utility remains unclear. We analyzed the brain activity of human participants as they performed a task involving choosing whether to receive information predictive of future pleasant outcomes. Using a computational model, we show three brain regions orchestrate anticipatory utility. Specifically, ventromedial prefrontal cortex tracks the value of anticipatory utility, dopaminergic midbrain correlates with information that enhances anticipation, while sustained hippocampal activity mediates a functional coupling between these regions. Our findings suggest a previously unidentified neural underpinning for anticipation’s influence over decision-making and unify a range of phenomena associated with risk and time-delay preference

Anomalous Dimensions of Non-Chiral Operators from AdS/CFT

Non-chiral operators with positive anomalous dimensions can have interesting applications to supersymmetric model building. Motivated by this, we develop a new method for obtaining the anomalous dimensions of non-chiral double-trace operators in N=1 superconformal field theories (SCFTs) with weakly-coupled AdS duals. Via the Hamiltonian formulation of AdS/CFT, we show how to directly compute the anomalous dimension as a bound state energy in the gravity dual. This simplifies previous approaches based on the four-point function and the OPE. We apply our method to a class of effective AdS5 supergravity models, and we find that the binding energy can have either sign. If such models can be UV completed, they will provide the first calculable examples of SCFTs with positive anomalous dimensions.Comment: 38 pages, 2 figures, refs adde

Superpotential de-sequestering in string models

Non-perturbative superpotential cross-couplings between visible sector matter and K\"ahler moduli can lead to significant flavour-changing neutral currents in compactifications of type IIB string theory. Here, we compute corrections to Yukawa couplings in orbifold models with chiral matter localised on D3-branes and non-perturbative effects on distant D7-branes. By evaluating a threshold correction to the D7-brane gauge coupling, we determine conditions under which the non-perturbative corrections to the Yukawa couplings appear. The flavour structure of the induced Yukawa coupling generically fails to be aligned with the tree-flavour structure. We check our results by also evaluating a correlation function of two D7-brane gauginos and a D3-brane Yukawa coupling. Finally, by calculating a string amplitude between n hidden scalars and visible matter we show how non-vanishing vacuum expectation values of distant D7-brane scalars, if present, may correct visible Yukawa couplings with a flavour structure that differs from the tree-level flavour structure.Comment: 37 pages + appendices, 8 figure

Bioorthogonal, Bifunctional Linker for Engineering Synthetic Glycoproteins

Post-translational glycosylation of proteins results in complex mixtures of heterogeneous protein glycoforms. Glycoproteins have many potential applications from fundamental studies of glycobiology to potential therapeutics, but generating homogeneous recombinant glycoproteins using chemical or chemoenzymatic reactions to mimic natural glycoproteins or creating homogeneous synthetic neoglycoproteins is a challenging synthetic task. In this work, we use a site-specific bioorthogonal approach to produce synthetic homogeneous glycoproteins. We develop a bifunctional, bioorthogonal linker that combines oxime ligation and strain-promoted azide–alkyne cycloaddition chemistry to functionalize reducing sugars and glycan derivatives for attachment to proteins. We demonstrate the utility of this minimal length linker by producing neoglycoprotein inhibitors of cholera toxin in which derivatives of the disaccharide lactose and GM1os pentasaccharide are attached to a nonbinding variant of the cholera toxin B-subunit that acts as a size- and valency-matched multivalent scaffold. The resulting neoglycoproteins decorated with GM1 ligands inhibit cholera toxin B-subunit adhesion with a picomolar IC50

Effectiveness of enhanced diabetes care to patients of South Asian ethnicity : the United Kingdom Asian Diabetes Study (UKADS) : a cluster randomised controlled trial

Background: Delivering high quality and evidence based healthcare to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive enhanced care package in UK general practice in improving cardiovascular risk factors in South Asian patients with type 2 diabetes. Methods: 21 inner city practices were randomised to intervention (enhanced practice nurse time, link worker and diabetes specialist nurse support) (n=868) or control (standard care) (n=618) groups. Prescribing algorithms with clearly defined targets were provided for all practices. Main outcome measures comprised changes in blood pressure, total cholesterol and glycaemic control (HbA1c) after 2 years. Findings: At baseline, groups were similar with respect to age, sex and cardiovascular risk factors. Comparing treatment groups, after adjustment for confounders, and clustering, differences in diastolic blood pressure (1.91mmHg, P=0.0001) and mean arterial pressure (1.36mmHg, P=0.0180) were significant. There were no significant differences between groups for total cholesterol or HbA1c. Economic analysis indicates the nurse-led intervention was not cost-effective. Across the whole study population systolic blood pressure, diastolic blood pressure and cholesterol decreased significantly by 4.9mmHg, 3.8mmHg and 0.45mmol/L respectively, but there was no change in HbA1c. Interpretation: Additional, although limited, benefits were observed from our culturally enhanced care package over and above the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to maximise healthcare outcomes in South Asian patients with diabetes

Dark Radiation and Dark Matter in Large Volume Compactifications

We argue that dark radiation is naturally generated from the decay of the overall volume modulus in the LARGE volume scenario. We consider both sequestered and non-sequestered cases, and find that the axionic superpartner of the modulus is produced by the modulus decay and it can account for the dark radiation suggested by observations, while the modulus decay through the Giudice-Masiero term gives the dominant contribution to the total decay rate. In the sequestered case, the lightest supersymmetric particles produced by the modulus decay can naturally account for the observed dark matter density. In the non-sequestered case, on the other hand, the supersymmetric particles are not produced by the modulus decay, since the soft masses are of order the heavy gravitino mass. The QCD axion will then be a plausible dark matter candidate.Comment: 27 pages, 4 figures; version 3: version published in JHE

D-branes at Toric Singularities: Model Building, Yukawa Couplings and Flavour Physics

We discuss general properties of D-brane model building at toric singularities. Using dimer techniques to obtain the gauge theory from the structure of the singularity, we extract results on the matter sector and superpotential of the corresponding gauge theory. We show that the number of families in toric phases is always less than or equal to three, with a unique exception being the zeroth Hirzebruch surface. With the physical input of three generations we find that the lightest family of quarks is massless and the masses of the other two can be hierarchically separated. We compute the CKM matrix for explicit models in this setting and find the singularities possess sufficient structure to allow for realistic mixing between generations and CP violation.Comment: 55 pages, v2: typos corrected, minor comments adde