Ground Water Monitoring Project for Arkansas, Phase III

This report is composed of two parts. The first part is an interpretation of the pesticide and nitrate data collected in Woodruff County based on samples collected during 1994. Because there is an indication that there were hydrological differences between 1994 and 1995, and because most of the pesticide data is from 1994, this interpretive portion is restricted to 1994 data. Six wells initially sampled in 1994 that contained pesticides had continuing contamination in re-sampling in 1994 and 1995. Part II lists a seventh well in Woodruff County that contained pesticides in February and May of 199

Cooperative Multi-agent Bandits: Distributed Algorithms with Optimal Individual Regret and Constant Communication Costs

Recently, there has been extensive study of cooperative multi-agent multi-armed bandits where a set of distributed agents cooperatively play the same multi-armed bandit game. The goal is to develop bandit algorithms with the optimal group and individual regrets and low communication between agents. The prior work tackled this problem using two paradigms: leader-follower and fully distributed algorithms. Prior algorithms in both paradigms achieve the optimal group regret. The leader-follower algorithms achieve constant communication costs but fail to achieve optimal individual regrets. The state-of-the-art fully distributed algorithms achieve optimal individual regrets but fail to achieve constant communication costs. This paper presents a simple yet effective communication policy and integrates it into a learning algorithm for cooperative bandits. Our algorithm achieves the best of both paradigms: optimal individual regret and constant communication costs

On-Demand Communication for Asynchronous Multi-Agent Bandits

This paper studies a cooperative multi-agent multi-armed stochastic bandit problem where agents operate asynchronously -- agent pull times and rates are unknown, irregular, and heterogeneous -- and face the same instance of a K-armed bandit problem. Agents can share reward information to speed up the learning process at additional communication costs. We propose ODC, an on-demand communication protocol that tailors the communication of each pair of agents based on their empirical pull times. ODC is efficient when the pull times of agents are highly heterogeneous, and its communication complexity depends on the empirical pull times of agents. ODC is a generic protocol that can be integrated into most cooperative bandit algorithms without degrading their performance. We then incorporate ODC into the natural extensions of UCB and AAE algorithms and propose two communication-efficient cooperative algorithms. Our analysis shows that both algorithms are near-optimal in regret.Comment: Accepted by AISTATS 202

The Online Knapsack Problem with Departures

The online knapsack problem is a classic online resource allocation problem in networking and operations research. Its basic version studies how to pack online arriving items of different sizes and values into a capacity-limited knapsack. In this paper, we study a general version that includes item departures, while also considering multiple knapsacks and multi-dimensional item sizes. We design a threshold-based online algorithm and prove that the algorithm can achieve order-optimal competitive ratios. Beyond worst-case performance guarantees, we also aim to achieve near-optimal average performance under typical instances. Towards this goal, we propose a data-driven online algorithm that learns within a policy-class that guarantees a worst-case performance bound. In trace-driven experiments, we show that our data-driven algorithm outperforms other benchmark algorithms in an application of online knapsack to job scheduling for cloud computing

Nobiletin Affects Circadian Rhythms and Oncogenic Characteristics in a Cell-Dependent Manner

The natural product nobiletin is a small molecule, widely studied with regard to its therapeutic effects, including in cancer cell lines and tumors. Recently, nobiletin has also been shown to affect circadian rhythms via their enhancement, resulting in protection against metabolic syndrome. We hypothesized that nobiletin’s anti-oncogenic effects, such as prevention of cell migration and formation of anchorage independent colonies, are correspondingly accompanied by modulation of circadian rhythms. Concurrently, we wished to determine whether the circadian and anti-oncogenic effects of nobiletin differed across cancer cell lines. In this study, we assessed nobiletin’s circadian and therapeutic characteristics to ascertain whether these effects depend on cell line, which here also varied in terms of baseline circadian rhythmicity. Three cell culture models where nobiletin’s effects on cell proliferation and migration have been studied previously were evaluated: U2OS (bone osteosarcoma), which possesses robust circadian rhythms; MCF7 (breast adenocarcinoma), which has weak circadian rhythms; and MDA-MB-231 (breast adenocarcinoma), which is arrhythmic. We found that circadian, migration, and proliferative effects following nobiletin treatment were subtle in the U2OS and MCF7 cells. On the other hand, changes were clear in MDA-MB-231s, where nobiletin rescued rhythmicity and substantially reduced oncogenic features, specifically two-dimensional cell motility and anchorage-independent growth. Based on these results and those previously described, we posit that the effects of nobiletin are indeed cell-type dependent, and that a positive correlation may exist between nobiletin’s circadian and therapeutic effects

p16INK4A expression is frequently increased in periorbital and ocular squamous lesions

Backgroundp16 expression is a well established biomarker of cervical dysplasia and carcinoma arising from high risk human papilloma virus infection. Increased p16 expression is also seen in squamous neoplasms arising at other sites, including head, neck, and oropharyngeal tract. Squamous lesions are also frequently encountered at ocular surface and peri-orbital skin sites, but the prevalence of increased p16 expression in these lesions has been poorly studied.MethodsWe retrospectively surveyed 13 ocular surface and 16 orbital squamous lesions biopsied at UC San Diego Healthcare System and VA San Diego Healthcare System for p16 expression by immunohistochemistry. These cases included ocular surface lesions with diagnoses of conjunctival intraepithelial neoplasm (CIN) and squamous cell carcinoma in situ. Peri-orbital eyelid biopsies included lesions with diagnoses of SCCis and invasive squamous cell carcinoma. We performed multivariate logistic regression, followed by student's T-test or Fisher's exact test to determine if there were statistically significant associations between p16 immunoreactivity and patient age, gender, diagnosis, and ethnicity. Statistical significance was defined as p < 0.05.ResultsWe found an unexpectedly large prevalence of strong nuclear and cytoplasmic p16 immunoreactivity in our cases. Almost all of the ocular surface squamous lesions were diffusely positive for p16 expression (12/13). All of the periorbital lesions showed diffuse p16 immunoreactivity (16/16). Altogether, 28/29 lesions tested showed strong and diffuse p16 expression. We found no statistically significant correlation between p16 expression and patient age, gender, ethnicity, or diagnosis. In 6 of the peri-orbital biopsies, we had sufficient tissue to assess high-risk HPV expression by in situ hybridization. Interestingly, all of these cases were negative for HPV, despite strong p16 expression.ConclusionStrong p16 expression was observed in virtually all of the ocular surface and peri-orbital squamous neoplasms in our study. The relationship between p16 expression and HPV infection in ocular surface and peri-orbital sites requires further investigation

Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with loss of nuclear transactive response DNA-binding protein 43 (TDP-43). Here we identify that TDP-43 regulates expression of the neuronal growth-associated factor stathmin-2. Lowered TDP-43 levels, which reduce its binding to sites within the first intron of stathmin-2 pre-messenger RNA, uncover a cryptic polyadenylation site whose utilization produces a truncated, non-functional mRNA. Reduced stathmin-2 expression is found in neurons trans-differentiated from patient fibroblasts expressing an ALS-causing TDP-43 mutation, in motor cortex and spinal motor neurons from patients with sporadic ALS and familial ALS with GGGGCC repeat expansion in the C9orf72 gene, and in induced pluripotent stem cell (iPSC)-derived motor neurons depleted of TDP-43. Remarkably, while reduction in TDP-43 is shown to inhibit axonal regeneration of iPSC-derived motor neurons, rescue of stathmin-2 expression restores axonal regenerative capacity. Thus, premature polyadenylation-mediated reduction in stathmin-2 is a hallmark of ALS-FTD that functionally links reduced nuclear TDP-43 function to enhanced neuronal vulnerability

Influence of supramolecular forces on the linear viscoelasticity of gluten

Stress relaxation behavior of hydrated gluten networks was investigated by means of rheometry combined with μ-computed tomography (μ-CT) imaging. Stress relaxation behavior was followed over a wide temperature range (0–70 °C). Modulation of intermolecular bonds was achieved with urea or ascorbic acid in an effort to elucidate the presiding intermolecular interactions over gluten network relaxation. Master curves of viscoelasticity were constructed, and relaxation spectra were computed revealing three relaxation regimes for all samples. Relaxation commences with a well-defined short-time regime where Rouse-like modes dominate, followed by a power law region displaying continuous relaxation concluding in a terminal zone. In the latter zone, poroelastic relaxation due to water migration in the nanoporous structure of the network also contributes to the stress relief in the material. Hydrogen bonding between adjacent protein chains was identified as the determinant force that influences the relaxation of the networks. Changes in intermolecular interactions also resulted in changes in microstructure of the material that was also linked to the relaxation behavior of the networks

Discovery of a Novel Prolactin in Non-Mammalian Vertebrates: Evolutionary Perspectives and Its Involvement in Teleost Retina Development

BACKGROUND:The three pituitary hormones, viz. prolactin (PRL), growth hormone (GH) and somatolactin (SL), together with the mammalian placental lactogen (PL), constitute a gene family of hormones with similar gene structure and encoded protein sequences. These hormones are believed to have evolved from a common ancestral gene through several rounds of gene duplication and subsequent divergence. PRINCIPAL FINDINGS:In this study, we have identified a new PRL-like gene in non-mammalian vertebrates through bioinformatics and molecular cloning means. Phylogenetic analyses showed that this novel protein is homologous to the previously identified PRL. A receptor transactivation assay further showed that this novel protein could bind to PRL receptor to trigger the downstream post-receptor event, indicating that it is biologically active. In view of its close phylogenetic relationship with PRL and also its ability to activate PRL receptor, we name it as PRL2 and the previously identified PRL as PRL1. All the newly discovered PRL2 sequences possess three conserved disulfide linkages with the exception of the shark PRL2 which has only two. In sharp contrast to the classical PRL1 which is predominantly expressed in the pituitary, PRL2 was found to be mainly expressed in the eye and brain of the zebrafish but not in the pituitary. A largely reduced inner nuclear layer of the retina was observed after morpholino knockdown of zebrafish PRL2, indicating its role on retina development in teleost. SIGNIFICANCE:The discovery of this novel PRL has revitalized our understanding on the evolution of the GH/PRL/SL/PL gene family. Its unique expression and functions in the zebrafish eye also provide a new avenue of research on the neuroendocrine control of retina development in vertebrates