Overfitting and forecasting: linear versus non-linear time series models

The main purpose of this dissertation is to compare the in-sample estimating and out-of-sample forecasting performance of a set of non-linear time series models, i.e., threshold autoregressive models, momentum threshold autoregressive models, exponential autoregressive models, generalized autoregressive models and bilinear models. First, a Monte Carlo simulation is used to study overfitting and forecasting. For AR processes, if the AIC and SBC criteria are used to select models, the possibility of overfitting is very high since the non-linear models and other linear models are very likely to have lower AIC and SBC. However, the MSPE for one-step ahead out-of-sample forecast can be used to identify the true AR processes. For TAR processes, the AIC can be used to identify the TAR-C models. The SBC and MSPE can identify the TAR process only if the difference of the persistence between the two regimes is large enough. Underfitting and misspecification are very likely to happen for a TAR process with small difference of the persistence between the two regimes. However, if we don\u27t know the true AR or TAR process, the MSPE can\u27t select the AR or TAR models in most cases. Thus, none of the AIC, SBC and MSPE can select the AR model for a given AR process with unknown order. For the TAR process, the AIC can consistently identify the TAR-C process and the SBC can identify the TAR-C process only if the difference of the persistency is large enough. Then, a set of linear and non-linear time series models are applied to the term structure of interest rates and the spread of wholesale and retail pork prices in U.S. It is shown that there are non-linear time series models can do better than the conventional ARMA models for both in-sample estimation and out-of-sample forecast. Also, it is very unlikely that the dominance of the non-linear time series models results from overfitting for both the term structure of interest rates and the spread of wholesale and retail pork prices in U.S. Thus, non-linear time series models are very useful for estimating and forecasting the non-linear time series

High Thermoelectric Figure of Merit by Resonant Dopant in Half-Heusler Alloys

Half-Heusler alloys have been one of the benchmark high temperature thermoelectric materials owing to their thermal stability and promising figure of merit ZT. Simonson et al. early showed that small amounts of vanadium doped in Hf0.75Zr0.25NiSn enhanced the Seebeck coefficient and correlated the change with the increased density of states near the Fermi level. We herein report a systematic study on the role of vanadium (V), niobium (Nb), and tantalum (Ta) as prospective resonant dopants in enhancing the ZT of n-type half-Heusler alloys based on Hf0.6Zr0.4NiSn0.995Sb0.005. The V doping was found to increase the Seebeck coefficient in the temperature range 300-1000 K, consistent with a resonant doping scheme. In contrast, Nb and Ta act as normal n-type dopants, as evident by the systematic decrease in electrical resistivity and Seebeck coefficient. The combination of enhanced Seebeck coefficient due to the presence of V resonant states and the reduced thermal conductivity has led to a state-of-the-art ZT of 1.3 near 850 K in n-type (Hf0.6Zr0.4)0.99V0.01NiSn0.995Sb0.005 alloys.Comment: Submitted to AIP Advance

Nuclear Factor κB and Anesthetic Preconditioning during Myocardial Ischemia-Reperfusion

BackgroundVolatile anesthetic preconditioning (APC) protects against myocardial ischemia-reperfusion (IR) injury, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism of APC in myocardial protection, the activation of nuclear factor (NF) kappaB and its regulated inflammatory mediators expression were examined in the current study.MethodsHearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-kappaB activity was determined by electrophoretic mobility shift assay. The NF-kappaB inhibitor, IkappaB-alpha, was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor alpha, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis.ResultsNuclear factor kappaB-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic IkappaB-alpha was decreased. Supershift assay revealed the involvement of NF-kappaB p65 and p50 subunits. APC with sevoflurane attenuated NF-kappaB activation and reduced the expression of tumor necrosis factor alpha, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR.ConclusionsThe results of this study indicate that attenuation of NF-kappaB activation and subsequent down-regulation of NF-kappaB-dependent inflammatory gene expression plays an important role in the protective mechanism of APC against acute myocardial IR injury

Multilayer perceptron-based literature reading preferences predict anxiety and depression in university students

ObjectiveThis study aims to precisely model the nonlinear relationship between university students’ literature reading preferences (LRP) and their levels of anxiety and depression using a multilayer perceptron (MLP) to identify reading-related risk factors affecting anxiety and depression among university students.MethodsIn this cross-sectional study, an internet-based questionnaire was conducted among 2,092 undergraduate students (aged 18–22, 62.7% female, from seven provinces in China). Participants completed a customized questionnaire on their LRP, followed by standardized assessments of anxiety and depression using the Generalized Anxiety Disorder 7-item Scale and the Beck Depression Inventory, respectively. An MLP with residual connections was employed to establish the nonlinear relationship between LRP and anxiety and depression.ResultsThe MLP model achieved an average accuracy of 86.8% for predicting non-anxious individuals and 81.4% for anxious individuals. In the case of depression, the model’s accuracy was 90.1% for non-depressed individuals and 84.1% for those with depression. SHAP value analysis identified “Tense/Suspenseful-Emotional Tone,” “War and Peace-Thematic Content,” and “Infrequent Reading-Reading Habits” as the top contributors to anxiety prediction accuracy. Similarly, “Sad-Emotional Tone Preference,” “Emotional Depictions-Thematic Content,” and “Thought-Provoking-Emotional Tone” were the primary contributors to depression prediction accuracy.ConclusionThe MLP accurately models the nonlinear relationship between LRP and mental health in university students, indicating the significance of specific reading preferences as risk factors. The study underscores the importance of literature emotional tone and themes in mental health. LRP should be integrated into psychological assessments to help prevent anxiety and depression among university students

Light Field Saliency Detection with Deep Convolutional Networks

Light field imaging presents an attractive alternative to RGB imaging because of the recording of the direction of the incoming light. The detection of salient regions in a light field image benefits from the additional modeling of angular patterns. For RGB imaging, methods using CNNs have achieved excellent results on a range of tasks, including saliency detection. However, it is not trivial to use CNN-based methods for saliency detection on light field images because these methods are not specifically designed for processing light field inputs. In addition, current light field datasets are not sufficiently large to train CNNs. To overcome these issues, we present a new Lytro Illum dataset, which contains 640 light fields and their corresponding ground-truth saliency maps. Compared to current light field saliency datasets [1], [2], our new dataset is larger, of higher quality, contains more variation and more types of light field inputs. This makes our dataset suitable for training deeper networks and benchmarking. Furthermore, we propose a novel end-to-end CNN-based framework for light field saliency detection. Specifically, we propose three novel MAC (Model Angular Changes) blocks to process light field micro-lens images. We systematically study the impact of different architecture variants and compare light field saliency with regular 2D saliency. Our extensive comparisons indicate that our novel network significantly outperforms state-of-the-art methods on the proposed dataset and has desired generalization abilities on other existing datasets.Comment: 14 pages, 14 figure

Stress-Driven Selection of Novel Phenotypes

A process has been developed that can confer novel properties, such as metal resistance, to a host bacterium. This same process can also be used to produce RNAs and peptides that have novel properties, such as the ability to bind particular compounds. It is inherent in the method that the peptide or RNA will behave as expected in the target organism. Plasmid-born mini-gene libraries coding for either a population of combinatorial peptides or stable, artificial RNAs carrying random inserts are produced. These libraries, which have no bias towards any biological function, are used to transform the organism of interest and to serve as an initial source of genetic variation for stress-driven evolution. The transformed bacteria are propagated under selective pressure in order to obtain variants with the desired properties. The process is highly distinct from in vitro methods because the variants are selected in the context of the cell while it is experiencing stress. Hence, the selected peptide or RNA will, by definition, work as expected in the target cell as the cell adapts to its presence during the selection process. Once the novel gene, which produces the sought phenotype, is obtained, it can be transferred to the main genome to increase the genetic stability in the organism. Alternatively, the cell line can be used to produce novel RNAs or peptides with selectable properties in large quantity for separate purposes. The system allows for easy, large-scale purification of the RNAs or peptide products. The process has been reduced to practice by imposing sub-inhibitory concentrations of NiCl2 on cells of the bacterium Escherichia coli that were transformed separately with the peptide library and RNA library. The evolved resistant clones were isolated, and sequences of the selected mini-gene variants were established. Clones resistant to NiCl2 were found to carry identical plasmid variants with a functional mini-gene that specifically conferred significant nickel tolerance on the host cells. Sequencing of the selected mini-gene revealed a propensity of the encoded peptide to bind transient metal ions. Expression of the mini-gene markedly improved growth parameters of the evolved clones at sub-inhibitory concentrations of NiCl2 while being slightly detrimental in the absence of stress. Similar results have been obtained with the RNA libraries. Overall, the results demonstrate a very natural outcome of the selection experiments in which the mini-genes were expected to be either successfully integrated into bacterial genetic networks, or rejected depending upon their effect on host fitness. This described approach can be useful as a laboratory model to study the dynamics of bacterial adaptive evolution on the molecular level. It can also provide a strategy for screening expressed DNA libraries in search of novel genes with desirable properties

Ibrutinib for B cell malignancies

Research over the role of Bruton’s agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr(223). This review discussed in details the role of BTK in B-cell signaling, molecular interactions between B cell lymphoma/leukemia cells and their microenvironment. Clinical trials of the novel BTK inhibitor, ibrutinib (PCI-32765), in B cell malignancies were summarized

Light Deficiency Inhibits Growth by Affecting Photosynthesis Efficiency as well as JA and Ethylene Signaling in Endangered Plant Magnolia sinostellata

The endangered plant Magnolia sinostellata largely grows in the understory of forest and suffers light deficiency stress. It is generally recognized that the interaction between plant development and growth environment is intricate; however, the underlying molecular regulatory pathways by which light deficiency induced growth inhibition remain obscure. To understand the physiological and molecular mechanisms of plant response to shading caused light deficiency, we performed photosynthesis efficiency analysis and comparative transcriptome analysis in M. sinostellata leaves, which were subjected to shading treatments of different durations. Most of the parameters relevant to the photosynthesis systems were altered as the result of light deficiency treatment, which was also confirmed by the transcriptome analysis. Gene Ontology and KEGG pathway enrichment analyses illustrated that most of differential expression genes (DEGs) were enriched in photosynthesis-related pathways. Light deficiency may have accelerated leaf abscission by impacting the photosynthesis efficiency and hormone signaling. Further, shading could repress the expression of stress responsive transcription factors and R-genes, which confer disease resistance. This study provides valuable insight into light deficiency-induced molecular regulatory pathways in M. sinostellata and offers a theoretical basis for conservation and cultivation improvements of Magnolia and other endangered woody plants

Establishment of Prostate Cancer Spheres from a Prostate Cancer Cell Line After Phenethyl Isothiocyanate Treatment and Discovery of androgen-Dependent Reversible Differentiation Between Sphere and Neuroendocrine Cells

Prostate cancer can transform from androgen-responsive to an androgen-independent phenotype. The mechanism responsible for the transformation remains unclear. We studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC), on the androgen-responsive LNCaP cells. After treatment with PEITC, floating spheres were formed with characteristics of prostate cancer stem cells (PCSC). These spheres were capable of self-renewal in media with and without androgen. They have been maintained in both types of media as long term cultures. Upon androgen deprivation, the adherent spheres differentiated to neuroendocrine cells (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC reverse differentiated to spheres when androgen was replenished. The sphere cells expressed surface marker CD44 and had enhanced histone H3K4 acetylation, DNMT1 down-regulation and GSTP1 activation. We hypothesize that PEITC-mediated alteration in epigenomics of LNCaP cells may give rise to sphere cells, whereas reversible androgenomic alterations govern the shuttling between sphere PCSC and progeny NEC. Our findings identify unrecognized properties of prostate cancer sphere cells with multi-potential plasticity. This system will facilitate development of novel therapeutic agents and allow further exploration into epigenomics and androgenomics governing the transformation to hormone refractory prostate cancer

DNAzyme-mediated recovery of small recombinant RNAs from a 5S rRNA-derived chimera expressed in Escherichia coli

Background: Manufacturing large quantities of recombinant RNAs by overexpression in a bacterial host is hampered by their instability in intracellular environment. To overcome this problem, an RNA of interest can be fused into a stable bacterial RNA for the resulting chimeric construct to accumulate in the cytoplasm to a sufficiently high level. Being supplemented with cost-effective procedures for isolation of the chimera from cells and recovery of the recombinant RNA from stabilizing scaffold, this strategy might become a viable alternative to the existing methods of chemical or enzymatic RNA synthesis. Results: Sequence encoding a 71-nucleotide recombinant RNA was inserted into a plasmid-borne deletion mutant of the Vibrio proteolyticus 5S rRNA gene in place of helix III - loop C segment of the original 5S rRNA. After transformation into Escherichia coli, the chimeric RNA (3譸en aRNA) was expressed constitutively from E. coli rrnB P1 and P2 promoters. The RNA chimera accumulated to levels that exceeded those of the host's 5S rRNA. A novel method relying on liquid solid partitioning of cellular constituents was developed for isolation of total RNA from bacterial cells. This protocol avoids toxic chemicals, and is therefore more suitable for large scale RNA purification than traditional methods. A pair of biotinylated 8-17 DNAzymes was used to bring about the quantitative excision of the 71-nt recombinant RNA from the chimera. The recombinant RNA was isolated by sequence-specific capture on beads with immobilized complementary deoxyoligonucleotide, while DNAzymes were recovered by biotin affinity chromatography for reuse. Conclusions:The feasibility of a fermentation-based approach for manufacturing large quantities of small RNAs in vivo using a "5S rRNA scaffold" strategy is demonstrated. The approach provides a route towards an economical method for the large-scale production of small RNAs including shRNAs, siRNAs and aptamers for use in clinical and biomedical research