Deep reinforcement learning for complex evaluation of one-loop diagrams in quantum field theory.

In this paper we present a technique based on deep reinforcement learning that allows for numerical analytic continuation of integrals that are often encountered in one-loop diagrams in quantum field theory. To extract certain quantities of two-point functions, such as spectral densities, mass poles or multiparticle thresholds, it is necessary to perform an analytic continuation of the correlator in question. At one-loop level in Euclidean space, this results in the necessity to deform the integration contour of the loop integral in the complex plane of the square of the loop momentum, to avoid nonanalyticities in the integration plane. Using a toy model for which an exact solution is known, we train a reinforcement learning agent to perform the required contour deformations. Our study shows great promise for an agent to be deployed in iterative numerical approaches used to compute nonperturbative two-point functions, such as the quark propagator Dyson-Schwinger equation, or more generally, Fredholm equations of the second kind, in the complex domain.

Creation of a Porcine Kyphotic Model.

STUDY DESIGN: Large animal study. OBJECTIVE: Create a thoracic hyperkyphotic deformity in an immature porcine spine, so that future researchers may use this model to validate spinal instrumentation and other therapies used in the treatment of hyperkyphosis. SUMMARY OF BACKGROUND DATA: Although several scoliotic animal models have been developed, there have been no reports of a thoracic hyperkyphotic animal model creation in an immature animal. The present study was designed to produce a porcine hyperkyphotic model by the time the pig weighed 25 kg, which corresponds to the approximate weight of a child undergoing surgery for early-onset scoliosis (EOS). METHODS: Successful surgical procedures were performed in 6 consecutive 10-kg (male, 5-week-old) immature Yorkshire pigs. Procedure protocol consisted of 1) a left thoracotomy at T10-T11, 2) screw placement at T9 and T11, 3) partial vertebrectomy at T10, 4) posterior interspinous ligament transection, and 5) placement of wire loop around screws and tightening. Weekly x-ray imaging was performed preoperatively and postoperatively, documenting progressively increasing kyphosis as the pig grew. Necropsy was performed 5-6 weeks after surgery, with CT, slab section, and histologic analysis. RESULTS: Average T9-T11 kyphosis (measured by sagittal Cobb angle) was 6.1° ± 1.4° (mean ± SD) preoperatively, 30.5° ± 1.0° immediately postoperation, and significantly increased to 50.3° ± 7.2° (p < .0001) over 5-6 weeks in 6 consecutive pigs at time of necropsy. CONCLUSIONS: An animal model of relatively more rigid-appearing thoracic hyperkyphotic deformities in immature pigs has been created. Subsequent studies addressing management of early-onset kyphosis with spinal instrumentation are now possible. LEVEL OF EVIDENCE: Level V.

Microtubule-associated protein-4 (MAP-4) inhibits microtubule-dependent distribution of mRNA in isolated neonatal cardiocytes.

OBJECTIVES: Active mRNA distribution in the form of ribonucleoprotein particles moving along microtubules has been shown in several cell types, but not yet in cardiocytes. This study addresses two hypotheses: 1) a similar mRNA distribution mechanism operates in cardiocytes; 2) decoration of microtubules with microtubule-associated proteins compromises this distribution. METHODS: To visualize ribonucleoproteins in cultured neonatal rat cardiocytes, they were transfected with vectors encoding zipcode binding protein-1 and Staufen fused with GFP. The velocity of microtubular transport and elongation were calculated on time-lapse confocal pictures. RESULTS: ZBP-1 and Staufen labeled particles co-localized with each other and with microtubules and moved along microtubules over a distance of 1-20 microm with a mean speed of 80 nm/s. The average speed decreased about 50% after decoration of microtubules by adenoviral microtubule-associated protein-4 (MAP-4). The elongation speed measured using the GFP-tagged end-binding protein-1 exceeded 200 nm/s and was not influenced by MAP-4. CONCLUSIONS: We demonstrate for the first time ribonucleoprotein particles in cardiocytes, their microtubular-related movement, and its inhibition (but not of the microtubular elongation), by the MAP-4 decoration of microtubules.

Isolation, purification, and full NMR assignments of cyclopamine from Veratrum californicum.

BACKGROUND: The Hedgehog signaling pathway is essential for embryogenesis and for tissue homeostasis in the adult. However, it may induce malignancies in a number of tissues when constitutively activated, and it may also have a role in other forms of normal and maladaptive growth. Cyclopamine, a naturally occurring steroidal alkaloid, specifically inhibits the Hedgehog pathway by binding directly to Smoothened, an important Hedgehog response element. To use cyclopamine as a tool to explore and/or inhibit the Hedgehog pathway in vivo, a substantial quantity is required, and as a practical matter cyclopamine has been effectively unavailable for usage in animals larger than mice. RESULTS: In this paper, we report a rapid and efficient isolation and purification of large quantities of cyclopamine from the roots and rhizomes of Veratrum californicum Dur. (the Corn Lily or Western false hellebore). We also provide unambiguous assignments of the carbon and proton resonances by using the multinuclear spectra and the spin coupling networks. CONCLUSION: This method could meet a very real need within diverse scientific communities by allowing cyclopamine to become more readily available.

Inhibition of beta-adrenergic receptor trafficking in adult cardiocytes by MAP4 decoration of microtubules.

Decreased beta-adrenergic receptor (beta-AR) number occurs both in animal models of cardiac hypertrophy and failure and in patients. beta-AR recycling is an important mechanism for the beta-AR resensitization that maintains a normal complement of cell surface beta-ARs. We have shown that 1) in severe pressure overload cardiac hypertrophy, there is extensive microtubule-associated protein 4 (MAP4) decoration of a dense microtubule network; and 2) MAP4 microtubule decoration inhibits muscarinic acetylcholine receptor recycling in neuroblastoma cells. We asked here whether MAP4 microtubule decoration inhibits beta-AR recycling in adult cardiocytes. [(3)H]CGP-12177 was used as a beta-AR ligand, and feline cardiocytes were isolated and infected with adenovirus containing MAP4 (AdMAP4) or beta-galactosidase (Adbeta-gal) cDNA. MAP4 decorated the microtubules extensively only in AdMAP4 cardiocytes. beta-AR agonist exposure reduced cell surface beta-AR number comparably in AdMAP4 and Adbeta-gal cardiocytes; however, after agonist withdrawal, the cell surface beta-AR number recovered to 78.4 +/- 2.9% of the pretreatment value in Adbeta-gal cardiocytes but only to 56.8 +/- 1.4% in AdMAP4 cardiocytes (P < 0.01). This result was confirmed in cardiocytes isolated from transgenic mice having cardiac-restricted MAP4 overexpression. In functional terms of cAMP generation, beta-AR agonist responsiveness of AdMAP4 cells was 47% less than that of Adbeta-gal cells. We conclude that MAP4 microtubule decoration interferes with beta-AR recycling and that this may be one mechanism for beta-AR downregulation in heart failure.