HCT116 colorectal liver metastases exacerbate muscle wasting in a mouse model for the study of colorectal cancer cachexia

Colorectal cancer (CRC) is often accompanied by formation of liver metastases (LM) and skeletal muscle wasting, i.e. cachexia. Despite affecting the majority of CRC patients, cachexia remains underserved, understudied and uncured. Animal models for the study of CRC-induced cachexia, in particular models containing LM, are sparse; therefore, we aimed to characterize two new models of CRC cachexia. Male NSG mice were injected subcutaneously (HCT116) or intrasplenically (mHCT116) with human HCT116 CRC tumor cells to disseminate LM, whereas experimental controls received saline (n=5-8/group). Tumor growth was accompanied by loss of skeletal muscle mass (HCT116: -20%; mHCT116: -31%; quadriceps muscle) and strength (HCT116: -20%; mHCT116: -27%), with worsened loss of skeletal muscle mass in mHCT116 compared with HCT116 (gastrocnemius: -19%; tibialis anterior: -22%; quadriceps: -21%). Molecular analyses revealed elevated protein ubiquitination in HCT116, whereas mHCT116 also displayed elevated Murf1 and atrogin-1 expression, along with reduced mitochondrial proteins PGC1α, OPA1, mitofusin 2 and cytochrome C. Further, elevated IL6 levels were found in the blood of mHCT116 hosts, which was associated with higher phosphorylation of STAT3 in skeletal muscle. To clarify whether STAT3 was a main player in muscle wasting in this model, HCT116 cells were co-cultured with C2C12 myotubes. Marked myotube atrophy (-53%) was observed, along with elevated phospho-STAT3 levels (+149%). Conversely, inhibition of STAT3 signaling by means of a JAK/STAT3 inhibitor was sufficient to rescue myotube atrophy induced by HCT116 cells (+55%). Overall, our results indicate that the formation of LM exacerbates cachectic phenotype and associated skeletal muscle molecular alterations in HCT116 tumor hosts

Bootstrapping a Five-Loop Amplitude Using Steinmann Relations

The analytic structure of scattering amplitudes is restricted by Steinmann relations, which enforce the vanishing of certain discontinuities of discontinuities. We show that these relations dramatically simplify the function space for the hexagon function bootstrap in planar maximally supersymmetric Yang-Mills theory. Armed with this simplification, along with the constraints of dual conformal symmetry and Regge exponentiation, we obtain the complete five-loop six-particle amplitude.Comment: 5 pages, 2 figures, 1 impressive table, and 2 ancillary files. v2: a few clarifications and references added; version to appear in PR

The Double Pentaladder Integral to All Orders

We compute dual-conformally invariant ladder integrals that are capped off by pentagons at each end of the ladder. Such integrals appear in six-point amplitudes in planar N=4 super-Yang-Mills theory. We provide exact, finite-coupling formulas for the basic double pentaladder integrals as a single Mellin integral over hypergeometric functions. For particular choices of the dual conformal cross ratios, we can evaluate the integral at weak coupling to high loop orders in terms of multiple polylogarithms. We argue that the integrals are exponentially suppressed at strong coupling. We describe the space of functions that contains all such double pentaladder integrals and their derivatives, or coproducts. This space, a prototype for the space of Steinmann hexagon functions, has a simple algebraic structure, which we elucidate by considering a particular discontinuity of the functions that localizes the Mellin integral and collapses the relevant symbol alphabet. This function space is endowed with a coaction, both perturbatively and at finite coupling, which mixes the independent solutions of the hypergeometric differential equation and constructively realizes a coaction principle of the type believed to hold in the full Steinmann hexagon function space.Comment: 70 pages, 3 figures, 4 tables; v2, minor typo corrections and clarification

Heavy Quark Thermalization in Classical Lattice Gauge Theory: Lessons for Strongly-Coupled QCD

Thermalization of a heavy quark near rest is controlled by the correlator of two electric fields along a temporal Wilson line. We address this correlator within real-time, classical lattice Yang-Mills theory, and elaborate on the analogies that exist with the dynamics of hot QCD. In the weak-coupling limit, it can be shown analytically that the dynamics on the two sides are closely related to each other. For intermediate couplings, we carry out non-perturbative simulations within the classical theory, showing that the leading term in the weak-coupling expansion significantly underestimates the heavy quark thermalization rate. Our analytic and numerical results also yield a general understanding concerning the overall shape of the spectral function corresponding to the electric field correlator, which may be helpful in subsequent efforts to reconstruct it from Euclidean lattice Monte Carlo simulations.Comment: 22 pages. v2: a reference and clarifications added; published versio

A Protocol for Animal Assisted Therapy in a Midwestern Hospital

Animal Assisted Therapy (AAT) has been shown to improve physiological, psychological, social, and physical aspects of clients (Miller & Ingram, 2000; Diefenbeck, Bouffard, Matukaitis, Hastings & Coble, 2010). AAT increases an individual’s strength, cognition, range of motion, and balance (Miller & Ingram, 2000). The use of animals within therapy also decreases anxiety, heart rate, blood pressure, and pain while also improving attention and social participation (Diefenbeck et al., 2010). The role of animals within AAT provides the therapist with a unique tool to utilize in various aspects of therapy. Depending on the treatment plan, the therapist can utilize the animal in various ways in order to match the client’s physical or psychological needs. Treatment plans that utilize AAT to improve the client’s well-being, socialization, and activities of daily living have been proven to be effective through the use of walking, feeding, brushing, petting, and bathing the animal (Barak & Mavashev, 2001). Along with clients receiving benefits from AAT, therapy staff has also indicated benefits including increase in self-awareness, improved morale, and stress reductions as result of using animals as a tool for therapy (Rossetti, DeFabiis & Belpedio, 2008). Benefits of incorporating AAT into therapy have been documented throughout the literature, however, there are limited facilities in the Midwest that implement AAT and existing protocols have been written for recreational animal visits rather than goal directed therapy (Winkle & Jackson, 2012). An extensive literature review on the benefits and contraindications of AAT, the role of the interprofessional team using AAT, AAT policies and procedures, and implementation of an AAT program was conducted. Staff members at a Midwestern hospital interested in incorporating AAT into therapy also provided suggestions to the creation of this protocol. The purpose of this scholarly project was to provide occupational therapists and other health care professionals with a protocol for implementation of an AAT program into a neurological rehabilitation facility. The protocol includes an introduction to AAT, benefits of AAT, AAT incorporated into the occupational therapy practice framework, authorized AAT users, skills competency, policies and procedures, AAT requirements and eligibility, and an intervention guide for utilizing AAT

Fluctuation, dissipation, and thermalization in non-equilibrium AdS_5 black hole geometries

We give a simple recipe for computing dissipation and fluctuations (commutator and anti-commutator correlation functions) for non-equilibrium black hole geometries. The recipe formulates Hawking radiation as an initial value problem, and is suitable for numerical work. We show how to package the fluctuation and dissipation near the event horizon into correlators on the stretched horizon. These horizon correlators determine the bulk and boundary field theory correlation functions. In addition, the horizon correlators are the components of a horizon effective action which provides a quantum generalization of the membrane paradigm. In equilibrium, the analysis reproduces previous results on the Brownian motion of a heavy quark. Out of equilibrium, Wigner transforms of commutator and anti-commutator correlation functions obey a fluctuation-dissipation relation at high frequency.Comment: 28 pages, 6 figure

Colour-electric spectral function at next-to-leading order

The spectral function related to the correlator of two colour-electric fields along a Polyakov loop determines the momentum diffusion coefficient of a heavy quark near rest with respect to a heat bath. We compute this spectral function at next-to-leading order, O(alpha_s^2), in the weak-coupling expansion. The high-frequency part of our result (omega >> T), which is shown to be temperature-independent, is accurately determined thanks to asymptotic freedom; the low-frequency part of our result (omega << T), in which Hard Thermal Loop resummation is needed in order to cure infrared divergences, agrees with a previously determined expression. Our result may help to calibrate the overall normalization of a lattice-extracted spectral function in a perturbative frequency domain T << omega << 1/a, paving the way for a non-perturbative estimate of the momentum diffusion coefficient at omega -> 0. We also evaluate the colour-electric Euclidean correlator, which could be directly compared with lattice simulations. As an aside we determine the Euclidean correlator in the lattice strong-coupling expansion, showing that through a limiting procedure it can in principle be defined also in the confined phase of pure Yang-Mills theory, even if a practical measurement could be very noisy there.Comment: 38 page

New Representations of the Perturbative S-Matrix

We propose a new framework to represent the perturbative S-matrix which is well-defined for all quantum field theories of massless particles, constructed from tree-level amplitudes and integrable term-by-term. This representation is derived from the Feynman expansion through a series of partial fraction identities, discarding terms that vanish upon integration. Loop integrands are expressed in terms of "Q-cuts" that involve both off-shell and on-shell loop-momenta, defined with a precise contour prescription that can be evaluated by ordinary methods. This framework implies recent results found in the scattering equation formalism at one-loop, and it has a natural extension to all orders---even non-planar theories without well-defined forward limits or good ultraviolet behavior.Comment: 4+1 pages, 4 figure

Heavy quark diffusion in QCD and N=4 SYM at next-to-leading order

We present the full details of a calculation at next-to-leading order of the momentum diffusion coefficient of a heavy quark in a hot, weakly coupled, QCD plasma. Corrections arise at O(g_s); physically they represent interference between overlapping scatterings, as well as soft, electric scale (p ~ gT) gauge field physics, which we treat using the hard thermal loop (HTL) effective theory. In 3-color, 3-flavor QCD, the momentum diffusion constant of a fundamental representation heavy quark at NLO is kappa = (16\pi/3) alpha_s^2 T^3 (log(1/g) + 0.07428 + 1.9026 g). We extend the computation to a heavy fundamental representation ``probe'' quark in large N_c, N=4 Super Yang-Mills theory, where the result is kappa^{SYM}= (lambda^2 T^3)(6\pi) (log(1/\sqrt{\lambda}) + 0.4304 + 0.8010 \sqrt{lambda}) (where lambda=g_s^2 N_c is the t'Hooft coupling). In the absence of some resummation technique, the convergence of perturbation theory is poor.Comment: 40 pages, 14 figure