Weighted programming: A programming paradigm for specifying mathematical models

We study weighted programming, a programming paradigm for specifying mathematical models. More specifically, the weighted programs we investigate are like usual imperative programs with two additional features: (1) nondeterministic branching and (2) weighting execution traces. Weights can be numbers but also other objects like words from an alphabet, polynomials, formal power series, or cardinal numbers. We argue that weighted programming as a paradigm can be used to specify mathematical models beyond probability distributions (as is done in probabilistic programming). We develop weakest-precondition- and weakest-liberal-precondition-style calculi à la Dijkstra for reasoning about mathematical models specified by weighted programs. We present several case studies. For instance, we use weighted programming to model the ski rental problem - an optimization problem. We model not only the optimization problem itself, but also the best deterministic online algorithm for solving this problem as weighted programs. By means of weakest-precondition-style reasoning, we can determine the competitive ratio of the online algorithm on source code level

Bounded Model Checking for Probabilistic Programs

In this paper we investigate the applicability of standard model checking approaches to verifying properties in probabilistic programming. As the operational model for a standard probabilistic program is a potentially infinite parametric Markov decision process, no direct adaption of existing techniques is possible. Therefore, we propose an on-the-fly approach where the operational model is successively created and verified via a step-wise execution of the program. This approach enables to take key features of many probabilistic programs into account: nondeterminism and conditioning. We discuss the restrictions and demonstrate the scalability on several benchmarks

High-transition-temperature superconductivity in the absence of the magnetic-resonance mode

The fundamental mechanism that gives rise to high-transition-temperature (high-Tc) superconductivity in the copper oxide materials has been debated since the discovery of the phenomenon. Recent work has focussed on a sharp 'kink' in the kinetic energy spectra of the electrons as a possible signature of the force that creates the superconducting state. The kink has been related to a magnetic resonance and also to phonons. Here we report that infrared spectra of Bi2Sr2CaCu2O(8+d), (Bi-2212) show that this sharp feature can be separated from a broad background and, interestingly, weakens with doping before disappearing completely at a critical doping level of 0.23 holes per copper atom. Superconductivity is still strong in terms of the transition temperature (Tc approx 55 K), so our results rule out both the magnetic resonance peak and phonons as the principal cause of high-Tc superconductivity. The broad background, on the other hand, is a universal property of the copper oxygen plane and a good candidate for the 'glue' that binds the electrons.Comment: 4 pages, 3 figure

Temperature Treatment of Highly Porous Zirconium-Containing Metal-Organic Frameworks Extends Drug Delivery Release.

Utilizing metal-organic frameworks (MOFs) as a biological carrier can lower the amount of the active pharmaceutical ingredient (API) required in cancer treatments to provide a more efficacious therapy. In this work, we have developed a temperature treatment process for delaying the release of a model drug compound from the pores of NU-1000 and NU-901, while taking care to utilize these MOFs' large pore volume and size to achieve exceptional model drug loading percentages over 35 wt %. Video-rate super-resolution microscopy reveals movement of MOF particles when located outside of the cell boundary, and their subsequent immobilization when taken up by the cell. Through the use of optical sectioning structured illumination microscopy (SIM), we have captured high-resolution 3D images showing MOF uptake by HeLa cells over a 24 h period. We found that addition of a model drug compound into the MOF and the subsequent temperature treatment process does not affect the rate of MOF uptake by the cell. Endocytosis analysis revealed that MOFs are internalized by active transport and that inhibiting the caveolae-mediated pathway significantly reduced cellular uptake of MOFs. Encapsulation of an anticancer therapeutic, alpha-cyano-4-hydroxycinnamic acid (α-CHC), and subsequent temperature treatment produced loadings of up to 81 wt % and demonstrated efficacy at killing cells beyond the burst release effect.M.H.T. thanks the Gates Cambridge Trust for funding, S. Haddad, D. Vulpe and Dr. C. Hockings for helpful discussions, and Dr. J. McMillan at the Cambridge Advanced Imaging Centre (CAIC), University of Cambridge. D.F.-J. thanks the Royal Society for funding through a University Research Fellowship. O.K.F. and J.T.H. gratefully acknowledge DTRA for financial support (grant HDTRA-1-14-1-0014). C.F.K. acknowledges funding from the UK Engineering and Physical Sciences Research Council, EPSRC (grants EP/L015889/1 and EP/H018301/1), the Wellcome Trust (grants 3-3249/Z/16/Z and 089703/Z/09/Z) and the UK Medical Research Council, MRC (grants MR/K015850/1 and MR/K02292X/1), and Infinitus (China) Ltd. Computational work was supported by the Cambridge High Performance Computing Cluster, Darwin

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

We present the long-term results of 18 chemotherapy relapsed indolent (N=12) or transformed (N=6) NHL patients of a phase II anti-CD20 131I-tositumomab (Bexxar®) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with 131I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, 131I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46–70 months

Parity-Violating Hydrodynamics in 2+1 Dimensions

We study relativistic hydrodynamics of normal fluids in two spatial dimensions. When the microscopic theory breaks parity, extra transport coefficients appear in the hydrodynamic regime, including the Hall viscosity, and the anomalous Hall conductivity. In this work we classify all the transport coefficients in first order hydrodynamics. We then use properties of response functions and the positivity of entropy production to restrict the possible coefficients in the constitutive relations. All the parity-breaking transport coefficients are dissipationless, and some of them are related to the thermodynamic response to an external magnetic field and to vorticity. In addition, we give a holographic example of a strongly interacting relativistic fluid where the parity-violating transport coefficients are computable.Comment: 39+1 page

Complexity of case mix in a regional allergy service

<p>Abstract</p> <p>Background</p> <p>Currently in the United Kingdom (UK), there is a mismatch between limited financial resources and the large proportion of patients with suspected allergies actually being referred to specialist allergy clinics. To better understand the case mix of patients being referred, we audited referrals to a regional allergy service over an 8 year period.</p> <p>The main source of data was consultant letters to General Practitioners (GP) summarising the diagnosis of patients, archived from January 2002 to September 2009. Letters were reviewed, extracting the clinic date, doctor seen, gender, date of birth, postcode, GP, and diagnoses. Diagnoses were classified into seven groups and illustrative cases for each group noted.</p> <p>Findings</p> <p>Data from 2,028 new referrals with suspected allergy were analysed. The largest group of patients (43%) were diagnosed with a type I hypersensitivity. The other diagnostic groups were chronic idiopathic (spontaneous) urticaria (35%), suspected type I hypersensitivity but no allergen identified (8%), idiopathic (spontaneous) angioedema (8%), physical urticaria (2.5%), non-allergic symptoms (1.6%), type IV hypersensitivity (0.8%) and ACE inhibitor sensitivity (0.5%). Two thirds of patients seen were female with a higher percentage of female patients in the non type-I hypersensitivity group (71%) than the type 1 hypersensitivity (66%) (χ²= 5.1, 1df, <it>p = 0.024</it>). The type 1 hypersensitivity patients were younger than other patients (38 Vs 46 years, t = -10.8, <it>p < 0.001</it>)</p> <p>Conclusions</p> <p>This study highlights the complexity of specialist allergy practice and the large proportion of patients referred with non-type I hypersensitivities, chronic idiopathic (spontaneous) urticaria being by far the largest group. Such information is critical to inform commissioning decisions, define referral pathways and in primary care education.</p

On Stability and Transport of Cold Holographic Matter

We use gauge-gravity duality to study the stability of zero-temperature, finite baryon density states of N=4 supersymmetric SU(Nc) Yang-Mills theory coupled to a single massive fundamental-representation N=2 hypermultiplet in the large-Nc and large-coupling limits. In particular, we study the spectrum of mesons. The dual description is a probe D7-brane in anti-de Sitter space with a particular configuration of worldvolume fields. The meson spectrum is dual to the spectrum of fluctuations of worldvolume fields about that configuration. We use a combination of analytical and numerical techniques to compute the spectrum, including a special numerical technique designed to deal with singular points in the fluctuations' equations of motion. Despite circumstantial evidence that the system might be unstable, such as a finite entropy density at zero temperature and the existence of instabilities in similar theories, we find no evidence of any instabilities, at least for the ranges of frequency and momenta that we consider. We discover a pole on the imaginary frequency axis in a scalar meson two-point function, similar to the diffusive mode in the two-point function of a conserved charge.Comment: 40 pages, 7 figure

Functional MRI in Awake Unrestrained Dogs

Because of dogs' prolonged evolution with humans, many of the canine cognitive skills are thought to represent a selection of traits that make dogs particularly sensitive to human cues. But how does the dog mind actually work? To develop a methodology to answer this question, we trained two dogs to remain motionless for the duration required to collect quality fMRI images by using positive reinforcement without sedation or physical restraints. The task was designed to determine which brain circuits differentially respond to human hand signals denoting the presence or absence of a food reward. Head motion within trials was less than 1 mm. Consistent with prior reinforcement learning literature, we observed caudate activation in both dogs in response to the hand signal denoting reward versus no-reward

No supra-additive effects of goserelin and radiotherapy on clonogenic survival of prostate carcinoma cells in vitro

<p>Abstract</p> <p>Background</p> <p>Oncological results of radiotherapy for locally advanced prostate cancer (PC) are significantly improved by simultaneous application of LHRH analoga (e.g. goserelin). As 85% of PC express LHRH receptors, we investigated the interaction of goserelin incubation with radiotherapy under androgen-deprived conditions in vitro.</p> <p>Methods</p> <p>LNCaP and PC-3 cells were stained for LHRH receptors. Downstream the LHRH receptor, changes in protein expression of c-fos, phosphorylated p38 and phosphorylated ERK1/2 were analyzed by means of Western blotting after incubation with goserelin and irradiation with 4 Gy. Both cell lines were incubated with different concentrations of goserelin in hormone-free medium. 12 h later cells were irradiated (0 – 4 Gy) and after 12 h goserelin was withdrawn. Endpoints were clonogenic survival and cell viability (12 h, 36 h and 60 h after irradiation).</p> <p>Results</p> <p>Both tested cell lines expressed LHRH-receptors. Changes in protein expression demonstrated the functional activity of goserelin in the tested cell lines. Neither in LNCaP nor in PC-3 any significant effects of additional goserelin incubation on clonogenic survival or cell viability for all tested concentrations in comparison to radiation alone were seen.</p> <p>Conclusion</p> <p>The clinically observed increase in tumor control after combination of goserelin with radiotherapy in PC cannot be attributed to an increase in radiosensitivity of PC cells by goserelin in vitro.</p