Text2Action: Generative Adversarial Synthesis from Language to Action

In this paper, we propose a generative model which learns the relationship between language and human action in order to generate a human action sequence given a sentence describing human behavior. The proposed generative model is a generative adversarial network (GAN), which is based on the sequence to sequence (SEQ2SEQ) model. Using the proposed generative network, we can synthesize various actions for a robot or a virtual agent using a text encoder recurrent neural network (RNN) and an action decoder RNN. The proposed generative network is trained from 29,770 pairs of actions and sentence annotations extracted from MSR-Video-to-Text (MSR-VTT), a large-scale video dataset. We demonstrate that the network can generate human-like actions which can be transferred to a Baxter robot, such that the robot performs an action based on a provided sentence. Results show that the proposed generative network correctly models the relationship between language and action and can generate a diverse set of actions from the same sentence.Comment: 8 pages, 10 figure

A Financial Assessment of Municipal Fiber in the U.S.

In the interest of bringing high-speed broadband access to communities underserved by current Internet service providers, many U.S. cities have initiated municipal broadband projects. Such efforts have received favorable attention from those eager to help close the digital divide. This brief presents a first look at a new, comprehensive empirical analysis of 20 U.S. municipal fiber builds for which financial data is available. The findings show that half of the projects in this study are cash-flow negative, and based on their performance from 2010-2014, 90 percent are unable to generate sufficient cash to recover their project costs within the 30-40 year life expectancy of a municipal fiber build. City leaders considering such projects, as well as state and federal officials interested in supporting them, need to understand the documented costs and risks before encouraging new municipal fiber programs to form.https://repository.upenn.edu/pennwhartonppi/1047/thumbnail.jp

Municipal Fiber in the United States: A Financial Assessment

Despite growing interest in broadband provided by municipally owned and operated fiber-to-the-home networks, the academic literature has yet to undertake a systematic assessment of these projects’ financial performance. To fill this gap, we utilize municipalities’ official reports to offer an empirical evaluation of the financial performance of every municipal fiber project in the U.S. operating in 2010 through 2019. An analysis of the actual performance of the resulting fifteen-project panel dataset reveals that none of the projects generated sufficient nominal cash flow in the short run to maintain solvency without infusions of additional cash from outside sources or debt relief. Similarly, 87% have not actually generated sufficient nominal cash flow to put them on track to achieve long-run solvency. In addition, 73% generated negative nominal cash flow over the past three fiscal years, leaving them poorly positioned to make up their deficits and causing them to fall farther into debt. An assessment based on the net present value of these projects’ operating cash flow indicates that 53% of projects would not be on track to breakeven even assuming the theoretical best-case performance in terms of capital expenditures and debt service. Close analysis of these projects’ performance reveals that revenue generation likely plays a more important role in generating cash flow than efficiency in construction costs or operating efficiency

Therapeutic laquinimod treatment decreases inflammation, initiates axon remyelination, and improves motor deficit in a mouse model of multiple sclerosis.

BackgroundTherapeutic strategies that induce effective neuroprotection and enhance intrinsic repair mechanisms are central goals for future treatment of multiple sclerosis (MS), as well as other diseases. Laquinimod (LQ) is an orally administered, central nervous system (CNS)-active immunomodulator with demonstrated efficacy in MS clinical trials and a favorable safety and tolerability profile.AimsWe aimed to explore the pathological, functional, and behavioral consequences of prophylactic and therapeutic (after presentation of peak clinical disease) LQ treatment in the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS.Materials and methodsActive EAE-induced 8-week-old C57BL/6 mice were treated with 5 or 25 mg/kg/day LQ via oral gavage beginning on EAE post-immunization day 0, 8, or 21. Clinical scores and rotorod motor performance were assessed throughout the disease course. Immune analysis of autoantigen-stimulated splenocytes, electrophysiological conduction of callosal axons, and immunohistochemistry of white matter-rich corpus callosum and spinal cord were performed.ResultsProphylactic and therapeutic treatment with LQ significantly decreased mean clinical disease scores, inhibited Th1 cytokine production, and decreased the CNS inflammatory response. LQ-induced improvement in axon myelination and integrity during EAE was functional, as evidenced by significant recovery of callosal axon conduction and axon refractoriness and pronounced improvement in rotorod motor performance. These improvements correlate with LQ-induced attenuation of EAE-induced demyelination and axon damage, and improved myelinated axon numbers.DiscussionEven when initiated at peak disease, LQ treatment has beneficial effects within the chronic EAE mouse model. In addition to its immunomodulatory effects, the positive effects of LQ treatment on oligodendrocyte numbers and myelin density are indicative of significant, functional neuroprotective and neurorestorative effects.ConclusionsOur results support a potential neuroprotective, in addition to immunomodulatory, effect of LQ treatment in inhibiting ongoing MS/EAE disease progression

A pragmatic evidence-based clinical management algorithm for burning mouth syndrome

Burning mouth syndrome is a poorly understood disease process with no current standard of treatment. The goal of this article is to provide an evidence-based, practical, clinical algorithm as a guideline for the treatment of burning mouth syndrome. Using available evidence and clinical experience, a multi-step management algorithm was developed. A retrospective cohort study was then performed, following STROBE statement guidelines, comparing outcomes of patients who were managed using the algorithm and those who were managed without. Forty-seven patients were included in the study, with 21 (45%) managed using the algorithm and 26 (55%) managed without. The mean age overall was 60.4 ±16.5 years, and most patients (39, 83%) were female. Cohorts showed no statistical difference in age, sex, overall follow-up time, dysgeusia, geographic tongue, or psychiatric disorder; xerostomia, however, was significantly different, skewed toward the algorithm group. Significantly more non-algorithm patients did not continue care (69% vs. 29%, p=0.001). The odds ratio of not continuing care for the non-algorithm group compared to the algorithm group was 5.6 [1.6, 19.8]. Improvement in pain was significantly more likely in the algorithm group (p=0.001), with an odds ratio of 27.5 [3.1, 242.0]. We present a basic clinical management algorithm for burning mouth syndrome which may increase the likelihood of pain improvement and patient follow-up

Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

Parkinson’s disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson’s disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology

ELF3 controls thermoresponsive growth in Arabidopsis

Plant development is highly responsive to ambient temperature, and this trait has been linked to the ability of plants to adapt to climate change [1]. The mechanisms by which natural populations modulate their thermoresponsiveness are not known [2]. To address this, we surveyed Arabidopsis accessions for variation in thermal responsiveness of elongation growth and mapped the corresponding loci. We find that the transcriptional regulator EARLY FLOWERING3 (ELF3) controls elongation growth in response to temperature. Through a combination of modeling and experiments, we show that high temperature relieves the gating of growth at night, highlighting the importance of temperature-dependent repressors of growth. ELF3 gating of transcriptional targets responds rapidly and reversibly to changes in temperature. We show that the binding of ELF3 to target promoters is temperature dependent, suggesting a mechanism where temperature directly controls ELF3 activity

Burst mitofusin activation reverses neuromuscular dysfunction in murine CMT2A

Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causa

Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin

The chromosomal passenger complex (CPC) is a conserved, essential regulator of cell division. As such, significant anti–cancer drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB kinase subunit. The CPC is activated by AURKB-catalyzed autophosphorylation on multiple subunits, but how this regulates CPC interactions with other mitotic proteins remains unclear. We investigated the hydrodynamic behavior of the CPC in Xenopus laevis egg cytosol using sucrose gradient sedimentation and in HeLa cells using fluorescence correlation spectroscopy. We found that autophosphorylation of the CPC decreases its sedimentation coefficient in egg cytosol and increases its diffusion coefficient in live cells, indicating a decrease in mass. Using immunoprecipitation coupled with mass spectrometry and immunoblots, we discovered that inactive, unphosphorylated CPC interacts with nucleophosmin/nucleoplasmin proteins, which are known to oligomerize into pentamers and decamers. Autophosphorylation of the CPC causes it to dissociate from nucleophosmin/nucleoplasmin. We propose that nucleophosmin/nucleoplasmin complexes serve as chaperones that negatively regulate the CPC and/or stabilize its inactive form, preventing CPC autophosphorylation and recruitment to chromatin and microtubules in mitosis