Miracle-dz/UniFAR-FTUs huggingface dataset:
Dendritic Integration and Reciprocal Inhibition in the Retina

Title of Document: DENDRITIC INTEGRATION AND RECIPROCAL INHIBITION IN THE RETINA William N. Grimes, Ph.D., 2008 Directed By: Professor Robert Walker, Department of Chemical Physics The mammalian retina is capable of signaling over a vast range of mean light levels (~10 10 ). Such a large dynamic range is achieved by segregating signals into contrasting pathways and utilizing excitatory and inhibitory neural circuits. The goal of this study was to elucidate subcellular mechanisms responsible for shaping dendritic computation and reciprocal inhibition within the retinal circuitry. Amacrine cells make up a unique class of inhibitory interneurons which lack anatomically distinct input and output structures. Although these interneurons clearly play important roles in complex visual processing, there is relatively little known about the ~30 subtypes. A17 amacrine cells have been shown to shape the time course of visual signaling in vivo. Intuition might suggest that a wide field (~400 μm) interneuron, such as A17, would provide long range lateral inhibition or center surround inhibition. However, using multi-disciplinary approaches, we have uncovered multiple mechanisms which underlie dendritic integration and synaptic transmission in A17 that allow it to respond with a high degree of synapse specificity. Additionally, these mechanisms work in concert with post-synaptic mechanisms to extend the dynamic range of reciprocal inhibition in the inner retina.
Steroid Receptor RNA Activator Stimulates Proliferation as Well as Apoptosis In Vivo

ABSTRACT Steroid receptor RNA activator (SRA) is an RNA that coactivates steroid hormone receptor-mediated transcription in vitro. Its expression is strongly up-regulated in many human tumors of the breast, uterus, and ovary, suggesting a potential role in pathogenesis. To assess SRA function in vivo, a transgenic-mouse model was generated to enable robust human SRA expression by using the transcriptional activity of the mouse mammary tumor virus long terminal repeat. Transgenic SRA was expressed in the nuclei of luminal epithelial cells of the mammary gland and tissues of the male accessory sex glands. Distinctive evidence for SRA function in vivo was obtained from the elevated levels of estrogen-controlled expression of progesterone receptor in transgenic mammary glands. Although overexpression of SRA showed strong promoting activities on cellular proliferation and differentiation, no alterations progressed to malignancy. Epithelial hyperplasia was accompanied by increased apoptosis, and preneoplastic lesions were cleared by focal degenerative transformations. In bitransgenic mice, SRA also antagonized ras-induced tumor formation. This work indicates that although coactivation of steroid-dependent transcription by SRA is accompanied by a proliferative response, overexpression is not in itself sufficient to induce turmorigenesis. Our results underline an intricate relationship between the different physiological roles of steroid receptors in conjunction with the RNA activator in the regulation of development, tissue homeostasis, and reproduction.
Developing a Workflow Design Framework Based on Dataflow Analysis

One important step in workflow automation is to design a valid and efficient workflow model that accurately specifies the execution sequence of activities in a business process. The dataflow constraints, which define the data input and output of each activity in a business process, can be used to analyze the dependencies among different activities and determine a proper workflow model for a particular business process. The basic idea of applying dataflow analysis to workflow design has been suggested in the literature. In this paper, we present a framework for applying dataflow analysis to workflow design. Our contribution is threefold. First, we introduce several new instruments, such as activity dependency tree and condition-action table, for specifying the necessary workflow requirements. Furthermore, we develop various key algorithms for requirements analysis and workflow model generation. Third, a system architecture is provided as a roadmap for developing a dataflow-based workflow design tool.
Atorvastatin up-regulates TRIB3 independent of ATF4-CHOP pathway in atherosclerotic patients.

BACKGROUND Macrophage apoptosis triggered by endoplasmic reticulum (ER) stress contributes much to atherosclerosis, especially plaque vulnerability. Activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP)-Tribbles 3 (TRIB3) pathway is closely related to the ER stress. This study aimed to investigate the effect of atorvastatin on the ATF4-CHOP-TRIB3 pathway. METHODS Forty-seven patients were randomized into 80-mg and 20-mg atorvastatin group. Follow-up was performed at weeks 6 and 12, and complete blood chemistry, lipid assay and detection of 5 target genes (tumor protein 53, ATF4, C/EBP, CHOP and TRIB3) in monocytes/macrophages were conducted. Furthermore, the interaction between dosage and duration of therapy was evaluated. RESULTS After 12-week therapy, patients in both groups experienced significant reductions in ATF4 (P=0.038) and C/EBP (P=0.003) expressions. Tumor protein 53 (P=0.015) and TRIB3 (P=0.045) expressions increased markedly in 80-mg atorvastatin group. However, there was no significant difference in CHOP expression at three time-points and between atorvastatin groups. Moreover, there was no interaction between dosage and duration of therapy. CONCLUSIONS Atorvastatin has an effect on ER stress through ATF4-CHOP pathway. Atorvastatin at a high dose is more likely to increase TRIB3 expression, but this warrants further investigation.
INTERPRETATION OF THE RESULTS OF COMMON PRINCIPAL COMPONENTS ANALYSES

Abstract Common principal components (CPC) analysis is a new tool for the comparison of phenotypic and genetic variance-covariance matrices. CPC was developed as a method of data summarization, but frequently biologists would like to use the method to detect analogous patterns of trait correlation in multiple populations or species. To investigate the properties of CPC, we simulated data that reflect a set of causal factors. The CPC method performs as expected from a statistical point of view, but often gives results that are contrary to biological intuition. In general, CPC tends to underestimate the degree of structure that matrices share. Differences of trait variances and covariances due to a difference in a single causal factor in two otherwise identically structured datasets often cause CPC to declare the two datasets unrelated. Conversely, CPC could identify datasets as having the same structure when causal factors are different. Reordering of vectors before analysis can aid in the detection of patterns. We urge caution in the biological interpretation of CPC analysis results. Corresponding Editor: T. Kawecki
Identification of a functional antioxidant responsive element in the promoter of the Chinese hamster carbonyl reductase 3 (Chcr3) gene

CHCR3, a member of the short‐chain dehydrogenase/reductase superfamily, is a carbonyl reductase 3 enzyme in Chinese hamsters. Carbonyl reductase 3 in humans has been believed to involve the metabolism and/or pharmacokinetics of anthracycline drugs, and the mechanism underlying the gene regulation has been investigated. In this study, the nucleotide sequence of the Chcr3 promoter was originally determined, and its promoter activity was characterised. The proximal promoter region is TATA‐less and GC‐rich, similar to the promoter region of human carbonyl reductase 3. Cobalt stimulated the transcriptional activity of the Chcr3 gene. The results of a luciferase gene reporter assay demonstrated that cobalt‐induced stimulation required an antioxidant responsive element. Forced expression of Nrf2, the transcription factor that binds to antioxidant responsive elements, enhanced the transcriptional activity of the Chcr3 gene. These results suggest that cobalt induces the expression of the Chcr3 gene via the Nrf2‐antioxidant responsive element pathway.
The academician–practitioner gap in advertising

The existence of the academician–practitioner gap is readily acknowledged and widely discussed in the marketing/advertising literature. This paper analyses key writings on the nature of the academician–practitioner rift and proposes a new approach complementing the literature. The review identifies five prevailing explanations why miscommunication between academicians and practitioners exists: (1) the failure of academic knowledge dissemination systems; (2) problems with the knowledge content and knowledge form academicians produce; (3) counterproductive academic organisational systems; (4) questions of philosophy of science; and (5) practitioners’ inability and unwillingness to process academic information. The study concludes that one potential explanation is entirely missed in these accounts: the possibility that practitioners’ knowledge about how advertising works is an autonomous construct, which has its own rules and deep structure, and resists simple assimilation attempted by academicians. The study also complements the existing literature by basing the review on firm theoretical grounds: the authors apply the influential sociological theory of professionalisation. Finally, future directions for research investigation are suggested, which moves the predominantly normative discourse into the empirical world.
Clinicopathological and Prognostic Significance of p27 Expression in Oral Squamous Cell Carcinoma: A Meta-Analysis

Despite being already known that p27 can regulate cell proliferation, cell motility and apoptosis, the role of p27 expression in oral squamous cell carcinoma (OSCC) remains controversial. The purpose of this study was to comprehensively evaluate, with a meta-analysis, the clinicopathological and prognostic role of p27 expression in OSCC. A meta-analysis of eligible studies was performed to assess the effects of p27 expression on clinicopathological parameters and overall survival (OS) in patients with OSCC, using pooled relative risks with 95% confidence intervals. Heterogeneity and publication bias were also assessed. Fourteen studies involving a total of 1,010 patients met the inclusion criteria. Low p27 expression was significantly associated with advanced TNM stage (p<0.001), worse histology (p=0.025), and lymph node metastasis (p<0.001), but not with tumor size (p=0.181). The pooled RR of 0.743 (p=0.002) suggested that low p27 expression has a poor prognosis in patients with OSCC. A significant heterogeneity among studies was detected for lymph node status (χ2=34.60, I2=68.2%, p<0.001) and OS (χ2=14.86, I2=39.4%, p=0.095). We did not detect a significant publication bias in this meta-analysis. Our meta-analysis suggests that p27 expression status might be useful as a predictive biomarker in clinical practice, and might potently predict OS in OSCC patients.
RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis

ABSTRACT Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC.
A Symbiotic Brain-Machine Interface through Value-Based Decision Making

Background In the development of Brain Machine Interfaces (BMIs), there is a great need to enable users to interact with changing environments during the activities of daily life. It is expected that the number and scope of the learning tasks encountered during interaction with the environment as well as the pattern of brain activity will vary over time. These conditions, in addition to neural reorganization, pose a challenge to decoding neural commands for BMIs. We have developed a new BMI framework in which a computational agent symbiotically decoded users' intended actions by utilizing both motor commands and goal information directly from the brain through a continuous Perception-Action-Reward Cycle (PARC). Methodology The control architecture designed was based on Actor-Critic learning, which is a PARC-based reinforcement learning method. Our neurophysiology studies in rat models suggested that Nucleus Accumbens (NAcc) contained a rich representation of goal information in terms of predicting the probability of earning reward and it could be translated into an evaluative feedback for adaptation of the decoder with high precision. Simulated neural control experiments showed that the system was able to maintain high performance in decoding neural motor commands during novel tasks or in the presence of reorganization in the neural input. We then implanted a dual micro-wire array in the primary motor cortex (M1) and the NAcc of rat brain and implemented a full closed-loop system in which robot actions were decoded from the single unit activity in M1 based on an evaluative feedback that was estimated from NAcc. Conclusions Our results suggest that adapting the BMI decoder with an evaluative feedback that is directly extracted from the brain is a possible solution to the problem of operating BMIs in changing environments with dynamic neural signals. During closed-loop control, the agent was able to solve a reaching task by capturing the action and reward interdependency in the brain.
Cognitive and context "Tuning": Tools to break anti-ecological habits

The fact that people do not behave in the way they are expected to, does not have to do only with a lack of motivation and intention but also with cognitive processes that might interfere with this. Even if the person has an intention to perform an ecological behavior, there can be barriers and constraints that prevent the pro-ecological goal of being attained. Accordingly, one of the techniques that can be used to increase the success in attaining pro-ecological behavioral goals is the development of implementation intentions. However, this technique is sometime ineffectively used due to a disregard of contextual characteristics. To overcome this, we propose the use of context "tuning" as a means to increase the effectiveness of habit change in a habitual context and thus, promote new behaviors in this same context. By conducting two studies, we promoted changes in the salience of the means to attain a behavioral goal, in order to facilitate the desired response elicited by implementation intentions. This was assessed in an online shopping simulation (study 1), with organic and non-organic products to choose from, in two variations of the same habitual context: equal salience (equally salient organic and non-organic goals) and lower salience context(organic goals less salient). Results showed that implementation intentions benefited from context "tuning", with a higher number of organic products being chosen in the equal salience context compared to a lower salience context. In study 2, we used what we call cognitive "tuning," directed towards the modification of the mentally represented means-goal connections, to produce cognitive changes equivalent to the context changes. Results showed that, although this did not increase the context "tuning" effect success, it still allowed for it to be replicated. Moreover, it showed a pattern in which this cognitive "tuning" can be used as a "vaccine" to prevent habitual behavior to be performed.
Tragedy of the Coulombs: Federating Energy Storage for Tiny, Intermittently-Powered Sensors

Untethered sensing devices have, for decades, powered all system components (processors, sensors, actuators, etc) from a single shared energy store (battery or capacitor). When designing batteryless sensors that are powered by harvested energy, this traditional approach results in devices that charge slowly and that are more error prone, inflexible, and inefficient than they could be. This paper presents a novel federated approach to energy storage, called UFoP, that partitions and prioritizes harvested energy automatically into multiple isolated smaller energy stores (capacitors). UFoP simplifies task scheduling, enables efficient use of components with differing voltage requirements, and produces devices that charge more quickly under identical harvesting conditions than a traditional centralized approach. We have implemented a UFoP reference design and conducted extensive experimental evaluation, including a short deployment. Our experimental results using an MSP430-based prototype show that UFoP provides as much as 10% more computational availability, and as much as four times more radio availability than the centralized approach. For all applications and energy environments evaluated, UFoP harvested 0.7-10.2% more energy than the centralized equivalent; meaning UFoP adds zero energy overhead.
Affordances for manipulation of physical versus digital media on interactive surfaces

This work presents the results of a comparative study in which we investigate the ways manipulation of physical versus digital media are fundamentally different from one another. Participants carried out both a puzzle task and a photo sorting task in two different modes: in a physical 3-dimensional space and on a multi-touch, interactive tabletop in which the digital items resembled their physical counterparts in terms of appearance and behavior. By observing the interaction behaviors of 12 participants, we explore the main differences and discuss what this means for designing interactive surfaces which use aspects of the physical world as a design resource.
3F-3 Liquid Sensor Using SAW and SH-SAW on Quartz

One-chip sensor system using two different acoustic waves on ST-cut quartz is presented; one is shear horizontal surface acoustic wave (SH-SAW) and the other is surface acoustic wave (SAW). On the sensor chip, there is a SH-SAW delay-line that is composed of a transmitting interdigital transducer (IDT), receiving IDT and a biochemical reaction area in between them. And there is another IDT on the sensor chip, that can excite a Rayleigh type SAW to the biochemical reaction area in the direction normal to the SH-SAW propagation direction. In order to evaluate the performance of the SH-SAW delay-line sensor, C-reactive protein antibodies with different concentrations are provided to the biochemical reaction area. The phase change in the S21 response of the SH-SAW delay-line at a fixed frequency are measured on real-time and it is confirmed that different phase changes are obtained for different antibody concentrations. On the other hand, the one-chip quartz-based liquid-phase SH-SAW delay-line sensors with pumping and agitating functions using SAW are demonstrated
Variational manifold learning for speaker recognition

This paper presents a variational manifold learning for speaker recognition based on the probabilistic linear discriminant analysis (PLDA) using i-vectors. A latent variable model is introduced to compensate the constraints of the linearity in PLDA scoring and the high dimensionality in using i-vectors. A deep variational learning is formulated to jointly optimize three objectives including a regularization for variational distributions, a reconstruction based on PLDA and a manifold learning for neighbor embedding. A stochastic gradient variational Bayesian algorithm is developed to optimize the variational lower bound of log likelihood where the expectation in the objectives is estimated via a sampling method. Interestingly, the latent variables in the proposed variational manifold PLDA (vm-PLDA) are capable of decoding or reconstructing the i-vectors. The experiments on visualization and speaker recognition show the merits of vm-PLDA in manifold learning and classification.
On Natural Learning and Pruning in Multilayered Perceptrons

Several studies have shown that natural gradient descent for on-line learning is much more efficient than standard gradient descent. In this article, we derive natural gradients in a slightly different manner and discuss implications for batch-mode learning and pruning, linking them to existing algorithms such as Levenberg-Marquardt optimization and optimal brain surgeon. The Fisher matrix plays an important role in all these algorithms. The second half of the article discusses a layered approximation of the Fisher matrix specific to multilayered perceptrons. Using this approximation rather than the exact Fisher matrix, we arrive at much faster natural learning algorithms and more robust pruning procedures.
Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 32 full factorial design

Background: Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. Objective: The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. Materials and Methods: DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 32 full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Results: Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Conclusion: Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration.