Reducing the Dimensionality of Linear Quadratic Control Problems

In linear-quadratic control (LQC) problems with singular control cost matrix and/or singular transition matrix, we derive a reduction of the dimension of the Riccati matrix, simplifying iteration and solution. Employing a novel transformation, we show that, under a certain rank condition, the matrix of optimal feedback coefficients is linear in the reduced Riccati matrix. For a substantive class of problems, our technique permits scalar iteration, leading to simple analytical solution. By duality the technique can also be applied to Kalman filtering problems with a singular measurement error covariance matrix

Electrocortical components of anticipation and consumption in a monetary incentive delay task

In order to improve our understanding of the components that reflect functionally important processes during reward anticipation and consumption, we used principle components analyses (PCA) to separate and quantify averaged ERP data obtained from each stage of a modified monetary incentive delay (MID) task. Although a small number of recent ERP studies have reported that reward and loss cues potentiate ERPs during anticipation, action preparation, and consummatory stages of reward processing, these findings are inconsistent due to temporal and spatial overlap between the relevant electrophysiological components. Our results show three components following cue presentation are sensitive to incentive cues (N1, P3a, P3b). In contrast to previous research, reward‐related enhancement occurred only in the P3b, with earlier components more sensitive to break‐even and loss cues. During feedback anticipation, we observed a lateralized centroparietal negativity that was sensitive to response hand but not cue type. We also show that use of PCA on ERPs reflecting reward consumption successfully separates the reward positivity from the independently modulated feedback‐P3. Last, we observe for the first time a new reward consumption component: a late negativity distributed over the left frontal pole. This component appears to be sensitive to response hand, especially in the context of monetary gain. These results illustrate that the time course and sensitivities of electrophysiological activity that follows incentive cues do not follow a simple heuristic in which reward incentive cues produce enhanced activity at all stages and substages

The Residual GEM technique and its application to the southwestern Japan/East Sea

The standard gravest empirical mode (GEM) technique for utilizing hydrography in concert with integral ocean measurements performs poorly in the southwestern Japan/East Sea (JES) because of a spatially variable seasonal signal and a shallow thermocline. This paper presents a new method that combines the U.S. Navy\u27s Modular Ocean Data Assimilation System (MODAS) static climatology (which implicitly contains the mean seasonal signal) with historical hydrography to construct a “residual GEM” from which profiles of such parameters as temperature (T) and specific volume anomaly (δ) can be estimated from measurements of an integral quantity such as geopotential height or acoustic echo time (τ). This is called the residual GEM technique. In a further refinement, sea surface temperature (SST) measurements are included in the profile determinations. In the southwestern JES, profiles determined by the standard GEM technique capture 70% of the T variance and 64% of the δ variance, while the residual GEM technique using SST captures 89% of the T variance and 84% of the δ variance. The residual GEM technique was applied to optimally interpolated τ measurements from a two-dimensional array of pressure-gauge-equipped inverted echo sounders moored from June 1999 to July 2001 in the southwestern JES, resulting in daily 3D estimated fields of T and δ throughout the region. These estimates are compared with those from direct measurements and good agreement is found between them

Modeling Heterogeneous Peer Assortment Effects Using Finite Mixture Exponential Random Graph Models

This article develops a class of models called sender/receiver finite mixture exponential random graph models (SRFM-ERGMs). This class of models extends the existing exponential random graph modeling framework to allow analysts to model unobserved heterogeneity in the effects of nodal covariates and network features without a block structure. An empirical example regarding substance use among adolescents is presented. Simulations across a variety of conditions are used to evaluate the performance of this technique. We conclude that unobserved heterogeneity in effects of nodal covariates can be a major cause of misfit in network models, and the SRFM-ERGM approach can alleviate this misfit. Implications for the analysis of social networks in psychological science are discussed

Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable antitumor immunity in a mouse glioma model.

BackgroundToca 511 (vocimagene amiretrorepvec) is a retroviral replicating vector encoding an optimized yeast cytosine deaminase (CD). Tumor-selective expression of CD converts the prodrug, 5-fluorocytosine (5-FC), into the active chemotherapeutic, 5-fluorouracil (5-FU). This therapeutic approach is being tested in a randomized phase II/III trial in recurrent glioblastoma and anaplastic astrocytoma (NCT0241416). The aim of this study was to identify the immune cell subsets contributing to antitumor immune responses following treatment with 5-FC in Toca 511-expressing gliomas in a syngeneic mouse model.MethodsFlow cytometry was utilized to monitor and characterize the immune cell infiltrate in subcutaneous Tu-2449 gliomas in B6C3F1 mice treated with Toca 511 and 5-FC.ResultsTumor-bearing animals treated with Toca 511 and 5-FC display alterations in immune cell populations within the tumor that result in antitumor immune protection. Attenuated immune subsets were exclusive to immunosuppressive cells of myeloid origin. Depletion of immunosuppressive cells temporally preceded a second event which included expansion of T cells which were polarized away from Th2 and Th17 in the CD4+ T cell compartment with concomitant expansion of interferon gamma-expressing CD8+ T cells. Immune alterations correlated with clearance of Tu-2449 subcutaneous tumors and T cell-dependent protection from future tumor challenge.ConclusionsTreatment with Toca 511 and 5-FC has a concentrated effect at the site of the tumor which causes direct tumor cell death and alterations in immune cell infiltrate, resulting in a tumor microenvironment that is more permissive to establishment of a T cell mediated antitumor immune response

Temporal dissociation of phencyclidine: Induced locomotor and social alterations in rats using an automated homecage monitoring system – implications for the 3Rs and preclinical drug discovery

Background: Rodent behavioural assays are widely used to delineate the mechanisms of psychiatric disorders and predict the efficacy of drug candidates. Conventional behavioural paradigms are restricted to short time windows and involve transferring animals from the homecage to unfamiliar apparatus which induces stress. Additionally, factors including environmental perturbations, handling and the presence of an experimenter can impact behaviour and confound data interpretation. To improve welfare and reproducibility these issues must be resolved. Automated homecage monitoring offers a more ethologically relevant approach with reduced experimenter bias. Aim: To evaluate the effectiveness of an automated homecage system at detecting locomotor and social alterations induced by phencyclidine (PCP) in group-housed rats. PCP is an NMDA receptor antagonist commonly utilised to model aspects of schizophrenia. Methods: Rats housed in groups of 3 were implanted with radio frequency identification (RFID) tags. Each homecage was placed over a RFID reader baseplate for the automated monitoring of the social and locomotor activity of each individual rat. For all rats, we acquired homecage data for 24 h following administration of both saline and PCP (2.5 mg/kg). Results: PCP resulted in significantly increased distance travelled from 15 to 60 min post injection. Furthermore, PCP significantly enhanced time spent isolated from cage-mates and this asociality lasted from 60 to 105 min post treatment. Conclusions: Unlike conventional assays, in-cage monitoring captures the temporal duration of drug effects on multiple behaviours in the same group of animals. This approach could benefit psychiatric preclinical drug discovery though improved welfare and increased between-laboratory replicability

The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma

The cell's repertoire of transfer RNAs (tRNAs) has been linked to cancer. Recently, levels of the initiator methionine tRNA (tRNAiMet) in stromal fibroblasts have been shown to influence extracellular matrix (ECM) secretion to drive tumour growth and angiogenesis. Here we show that increased tRNAiMet within cancer cells does not influence tumour growth, but drives cell migration and invasion via a mechanism that is independent from ECM synthesis and dependent on α5β1 integrin and levels of the translation initiation ternary complex. In vivo and ex vivo migration (but not proliferation) of melanoblasts is significantly enhanced in transgenic mice which express additional copies of the tRNAiMet gene. We show that increased tRNAiMet in melanoma drives migratory, invasive behaviour and metastatic potential without affecting cell proliferation and primary tumour growth, and that expression of RNA polymerase III-associated genes (which drive tRNA expression) are elevated in metastases by comparison with primary tumours. Thus specific alterations to the cancer cell tRNA repertoire drive a migration/invasion programme that may lead to metastasis

The effects of graded levels of calorie restriction : III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse

GRANT SUPPORT This work was supported by BBSRC BB009953/1 awarded to JRS and SEM. PK and CD were funded by the Erasmus exchange programme. JRS, SEM, DD, CG, LC, JJDH, YW, DELP, DL and AD are members of the BBSRC China Partnership Award, BB/J020028/1.Peer reviewedPublisher PD