Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein Kinase Cδ-dependent Induction of Manganese Superoxide Dismutase Gene Expression by Microtubule-active Anticancer Drugs*

Bacterial lipopolysaccharide can induce manganese superoxide dismutase (MnSOD) gene expression in a variety of cells. Paclitaxel (taxol) shares many properties of lipopolysaccharide. Here we report that paclitaxel can induce MnSOD gene expression in human lung adenocarcinoma cell line A549 in a time- and dose-dependent manner. Additional anticancer drugs, vinblastine and vincristine, also induced MnSOD gene expression. We have shown previously (Das, K. C., and White, C. W. (1997)J. Biol. Chem. 272, 14914–14920) that these drugs can activate protein kinase C (PKC). The PKC agonists thymeleatoxin (0.5 μm) and 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA; 10 nm) potently induced MnSOD gene expression. Calphostin C and GF109203X, both specific inhibitors of PKC, each inhibited MnSOD gene expression by anticancer agents. Down-regulation of PKC by prolonged treatment with phorbol 12-myristate 13-acetate (PMA) also inhibited induction of MnSOD by anticancer drugs, indicating an important role of PKC in MnSOD signaling by these agents. Of 11 PKC isoenzymes, only PKCδ translocated to the cell membrane after stimulation with anticancer drugs. By contrast, dPPA, PMA, and thymeleatoxin caused translocation of PKCα, βI, δ, and μ isotypes. Anticancer drug-stimulated cells also had increased total PKC activity in membrane and cytosolic fractions. Thus, paclitaxel, vinblastine, and vincristine each specifically activate PKCδ, whereas PMA, thymeleatoxin, and dPPA activate multiple isoenzymes. PKCδ was the only isoform activated by each agent in both groups of compounds effective in MnSOD induction.
Concept Identification and Normalisation for Adverse Drug Event Discovery in Medical Forums

Social media is becoming an increasingly important source of information to complement traditional pharmacovigilance methods. In order to identify signals of potential adverse drug reactions, it is necessary to ﬁrst identify medical concepts and drugs in the text. We evaluate diﬀerent concept extraction techniques on medical forums and for the machine learning approaches we encode complex annotations using a scheme that showed good results in other domains. Our study shows that the extended encoding scheme, although imperfect, still produces good results despite the complexities of social media. The comparison of techniques shows that the machine learning approach signiﬁcantly outperforms the other approaches.
LQG Flight Control of VTAV for Enhanced Situational Awareness

— This paper focuses on a critical component of the situational awareness (SA), the control of autonomous vertical flight for vectored thrust aerial vehicle (VTAV). With the SA strategy, we proposed a linear-quadratic-Gaussian (LQG) flight control procedure for an unmanned helicopter model with vectored thrust configuration. This LQG control for chosen model of VTAV has been verified by simulation of take-off and landing maneuvers using software package Simulink and demonstrated good performance for fast flight stabilization of model, consequently, fast SA with economy in energy can be asserted during search-and-rescue operations.
Toward Never Ending Language Learning

We report research toward a never-ending language learning system, focusing on a first implementation which learns to classify occurrences of noun phrases according to lexical categories such as “city” and “university. ” Our experiments suggest that the accuracy of classifiers produced by semi-supervised learning can be improved by coupling the learning of multiple classes based on background knowledge about relationships between the classes (e.g., ”university” is mutually exclusive of ”company”, and is a subset of ”organization”).
A Time-Domain Reflectometry Method with Variable Needle Pulse Width for Measuring the Dielectric Properties of Materials

Time-domain reflectometry (TDR) methods used for measuring the dielectric properties of materials mostly utilize step or needle electrical pulses of constant amplitudes and shapes. Our novel approach enables determining the dielectric relaxation time of a sample using the analysis of the amplitudes of reflected pulses of two widths, in addition to bulk dielectric permittivity and electrical conductivity commonly obtained by the TDR technique. The method was developed for various values of electrical conductivity and relaxation time using numerical simulations of a five-rod probe placed in a material with complex dielectric permittivity described by the Debye model with an added electrical conductivity term. The characterization of amplitudes of two pulses of selected widths was done with regard to the dielectric parameters of simulated materials. The required probe parameters were obtained solely from numerical simulations. Verification was performed for the probe placed in aqueous KCl solutions with 14 different electrical conductivity values. The determined relaxation time remained roughly constant and independent of electrical conductivity. The obtained electrical conductivity agreed with the reference values. Our results indicate that the relaxation time, dielectric permittivity and electrical conductivity of the tested solutions can be simultaneously determined using a simple analysis of the amplitude and reflection time of two needle pulses of different widths.
Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy.

High interstitial fluid pressure (IFP) in solid tumors is associated with reduced blood flow as well as inadequate delivery of therapeutic agents such as monoclonal antibodies. In the present study, IFP was measured as a function of radial position within two rat tissue-isolated tumors (mammary adenocarcinoma R3230AC, 0.4-1.9 g, n = 9, and Walker 256 carcinoma, 0.5-5.0 g, n = 6) and a s.c. tumor (mammary adenocarcinoma R3230AC, 0.6-20.0 g, n = 7). Micropipettes (tip diameters 2 to 4 microns) connected to a servo-null pressure-monitoring system were introduced to depths of 2.5 to 3.5 mm from the tumor surface and IFP was measured while the micropipettes were retrieved to the surface. The majority (86%) of the pressure profiles demonstrated a large gradient in the periphery leading to a plateau of almost uniform pressure in the deeper layers of the tumors. Within isolated tumors, pressures reached plateau values at a distance of 0.2 to 1.1 mm from the surface. In s.c. tumors the sharp increase began in skin and levelled off at the skin-tumor interface. These results demonstrate for the first time that the IFP is elevated throughout the tumor and drops precipitously to normal values in the tumor's periphery or in the immediately surrounding tissue. These results confirm the predictions of our recently published mathematical model of interstitial fluid transport in tumors (Jain and Baxter, Cancer Res., 48: 7022-7032, 1988), offer novel insight into the etiology of interstitial hypertension, and suggest possible strategies for improved delivery of therapeutic agents.
Controlling an autonomous agent using internal value based action selection

In this paper we describe an approach of controlling an autonomous robot by means of a hierarchical control structure, with a learning action selection. Since Damasio's "Descartes' error" in 1994 the number of approaches to action selection that use internal values, derived from psychological models of emotions or drives has increased significantly. The approach realises a learning action selection mechanism in a hierarchy of sensory and actuatory layers. The sensory values yield the internal states, as a basis for action selection. In addition they are used to calculate the reinforcement signal that trains the action selection.
The Forward Kinematics of the 6-6 Stewart Platform Using Extra Sensors

To solve the forward kinematics is one of the major problems for the 6-dof parallel manipulators. The complexity of formulation and computational burden make the conventional methods hard to be implemented in practice. In this paper, the tetrahedron configurations are applied to solve the forward kinematics of the 6-6 Stewart platform. This method turns the forward kinematics to tetrahedron geometry with the advantages that it avoids to solve numerical iteration, and the solution is unique. This approach can be used in real time application for its simplicity. An experiment designed to compare the actual orientation of the moving platform and the forward kinematics solution is presented in this paper. It is found through the experiment that the proposed method can achieve real time application.
Impacts of Different Grades of Tropical Cyclones on Infectious Diarrhea in Guangdong, 2005-2011

Objective Guangdong province is one of the most vulnerable provinces to tropical cyclones in China. Most prior studies concentrated on the relationship between tropical cyclones and injuries and mortality. This study aimed to explore the impacts of different grades of tropical cyclones on infectious diarrhea incidence in Guangdong province, from 2005 to 2011. Methods Mann-Whitney U test was firstly used to examine if infectious diarrhea were sensitive to tropical cyclone. Then unidirectional 1:1 case-crossover design was performed to quantitatively evaluate the relationship between daily number of infectious diarrhea and tropical cyclone from 2005 to 2011 in Guangdong, China. Principal component analysis (PCA) was applied to eliminate multicollinearity. Multivariate logistic regression model was used to estimate the hazard ratios (HRs) and the 95% confidence intervals (CI). Results There were no significant relationships between tropical cyclone and bacillary dysentery, amebic dysentery, typhoid, and paratyphoid cases. Infectious diarrhea other than cholera, dysentery, typhoid and paratyphoid significantly increased after tropical cyclones. The strongest effect were shown on lag 1 day (HRs = 1.95, 95%CI = 1.22, 3.12) and no lagged effect was detected for tropical depression, tropical storm, severe tropical storm and typhoon, with the largest HRs (95%CI) of 2.16 (95%CI = 1.69, 2.76), 2.43 (95%CI = 1.65, 3.58) and 2.21 (95%CI = 1.65, 2.69), respectively. Among children below 5 years old, the impacts of all grades of tropical cyclones were strongest at lag 0 day. And HRs were 2.67 (95%CI = 1.10, 6.48), 2.49 (95%CI = 1.80, 3.44), 4.89 (95%CI = 2.37, 7.37) and 3.18 (95%CI = 2.10, 4.81), respectively. Conclusion All grades of tropical cyclones could increase risk of other infectious diarrhea. Severe tropical storm has the strongest influence on other infectious diarrhea. The impacts of tropical cyclones on children under 5 years old were higher than total population.
Climate and Dengue Transmission: Evidence and Implications

Background: Climate influences dengue ecology by affecting vector dynamics, agent development, and mosquito/human interactions. Although these relationships are known, the impact climate change will have on transmission is unclear. Climate-driven statistical and process-based models are being used to refine our knowledge of these relationships and predict the effects of projected climate change on dengue fever occurrence, but results have been inconsistent. Objective: We sought to identify major climatic influences on dengue virus ecology and to evaluate the ability of climate-based dengue models to describe associations between climate and dengue, simulate outbreaks, and project the impacts of climate change. Methods: We reviewed the evidence for direct and indirect relationships between climate and dengue generated from laboratory studies, field studies, and statistical analyses of associations between vectors, dengue fever incidence, and climate conditions. We assessed the potential contribution of climate-driven, process-based dengue models and provide suggestions to improve their performance. Results and Discussion: Relationships between climate variables and factors that influence dengue transmission are complex. A climate variable may increase dengue transmission potential through one aspect of the system while simultaneously decreasing transmission potential through another. This complexity may at least partly explain inconsistencies in statistical associations between dengue and climate. Process-based models can account for the complex dynamics but often omit important aspects of dengue ecology, notably virus development and host–species interactions. Conclusion: Synthesizing and applying current knowledge of climatic effects on all aspects of dengue virus ecology will help direct future research and enable better projections of climate change effects on dengue incidence. Citation: Morin CW, Comrie AC, Ernst KC. 2013. Climate and dengue transmission: evidence and implications. Environ Health Perspect 121:1264–1272; http://dx.doi. org/10.1289/ehp.1306556
Annual Changes in Bone Mineral Content and Body Composition during Growth

Objectives: To compute the annual changes in total bone mineral content (BMCt), lean tissue mass and fat mass (LTM and FM) during growth. Methods: Whole body DXA data were used to calculate the annual changes of the parameter P (P = BMCt, LTM or FM), as a percentage, as ΔP% = 100 × (Pi+1 – Pi) / Pi; with Pi and Pi+1 the values for P at age i and age (i+1). Smoothed curves were then obtained from ΔP% values plotted against age. Results: Changes in FM were different in males and females. A peak velocity was marked for the three tissues at age 6.5 in boys, and at age 6.5–7.5 in girls; a pubertal peak spurt appeared at age 12 in girls and between age 13 and 14 in boys. This latter peak was followed by an exponential decrease, and no significant changes were found for the three components after age 20 in girls and age 21–22 in boys. Conclusion: Changes in tissue accretion during growth are easy to follow when expressed in percentages. Fat changes, especially, should be around 17% in girls and 15% in boys at the age of puberty.
A C++ data model supporting reachability analysis and dead code detection

A software repository provides a central information source for understanding and reengineering code in a software project. Complex reverse engineering tools can be built by analyzing information stored in the repository without reparsing the original source code. The most critical design aspect of a repository is its data model, which directly affects how effectively the repository supports various analysis tasks. This paper focuses on the design rationales behind a data model for a C++ software repository that supports reachability analysis and dead code detection at the declaration level. These two tasks are frequently needed in large software projects to help remove excess software baggage, select regression tests, and support software reuse studies. The language complexity introduced by class inheritance, friendships, and template instantiations in C++ requires a carefully designed model to catch all necessary dependencies for correct reachability analysis. We examine the major design decisions and their consequences in our model and illustrate how future software repositories can be evaluated for completeness at a selected abstraction level. Examples are given to illustrate how our model also supports variants of reachability analysis: impact analysis, class visibility analysis, and dead code detection. Finally, we discuss the implementation and experience of our analysis tools on a C++ software project.
Clarification of the Mechanism of Acylation Reaction and Origin of Substrate Specificity of the Serine-carboxyl Peptidase Sedolisin through Qm/mm Free Energy Simulations

Quantum mechanical/molecular mechanical (QM/MM) free energy simulations are applied for understanding the mechanism of the acylation reaction catalyzed by sedolisin, a representative serine-carboxyl peptidase, leading to the acyl-enzyme (AE) and first product from the enzyme-catalyzed reaction. One of the interesting questions to be addressed in this work is the origin of the substrate specificity of sedolisin that shows a relatively high activity on the substrates with Glu at P 1 site. It is shown that the bond making and breaking events of the acylation reaction involving a peptide substrate (LLE*FL) seem to be accompanied by local conformational changes, proton transfers as well as the formation of alternative hydrogen bonds. The results of the simulations indicate that the conformational change of Glu at P 1 site and its formation of a low barrier hydrogen bond with Asp-170 (along with the transient proton transfer) during the acylation reaction might play a role in the relatively high specificity for the substrate with Glu at P 1 site. The role of some key residues in the catalysis is confirmed through free energy simulations. Glu-80 is found to act as a general base to accept a proton from Ser-287 during the nucleophilic attack and then as a general acid to protonate the leaving group (N-H of P 1 0-Phe) during the cleavage of the scissile peptide bond. Another acidic residue, Asp-170, acts as a general acid catalyst to protonate the carbonyl of P 1-Glu during the formation of the tetrahedral intermediate and as a general base for the formation of the acyl-enzyme. The energetic results from the free energy simulations support the importance of proton transfer from Asp-170 to the carbonyl of P 1-Glu in the stabilization of the tetrahedral intermediate and the formation of a low-barrier hydrogen bond between the carboxyl group of P 1-Glu and Asp-170 in the lowering of the free energy barrier for the cleavage of the peptide bond. Detailed analyses of the proton transfers during acylation are also given. ' INTRODUCTION Sedolisins (serine-carboxyl peptidases) belong to the family S53 of clan SB of serine peptidases (MEROPS S53). 1 The enzymes in this family share some common properties, including maximum activity at low pH (e.g., pH 3-5) and the presence of conserved acidic residues (aspartate and glutamate) required for the activity. 1c,2 The members of the family also include tripepti-dyl-peptidase 1 (TPP1) 3 for which the loss of the activity as …
Circulating MicroRNAs as Potential Biomarkers of Exercise Response

Systematic physical activity increases physical fitness and exercise capacity that lead to the improvement of health status and athletic performance. Considerable effort is devoted to identifying new biomarkers capable of evaluating exercise performance capacity and progress in training, early detection of overtraining, and monitoring health-related adaptation changes. Recent advances in OMICS technologies have opened new opportunities in the detection of genetic, epigenetic and transcriptomic biomarkers. Very promising are mainly small non-coding microRNAs (miRNAs). miRNAs post-transcriptionally regulate gene expression by binding to mRNA and causing its degradation or inhibiting translation. A growing body of evidence suggests that miRNAs affect many processes and play a crucial role not only in cell differentiation, proliferation and apoptosis, but also affect extracellular matrix composition and maintaining processes of homeostasis. A number of studies have shown changes in distribution profiles of circulating miRNAs (c-miRNAs) associated with various diseases and disorders as well as in samples taken under physiological conditions such as pregnancy or physical exercise. This overview aims to summarize the current knowledge related to the response of blood c-miRNAs profiles to different modes of exercise and to highlight their potential application as a novel class of biomarkers of physical performance capacity and training adaptation.
Relapse After Tibialis Anterior Tendon Transfer in Idiopathic Clubfoot Treated by the Ponseti Method

Background: The Ponseti method for clubfoot correction has demonstrated excellent results. However, relapses are common and continue to be the most important problem facing clubfoot practitioners. Relapses usually require repeated casting and/or surgical intervention with tibialis anterior tendon transfer (TATT). However, recent data on relapses suggest that performing a successful TATT may not be a definitive cure as there may be other processes, such as neuromuscular deficits, that may result in subsequent relapses. Methods: The authors reviewed 66 patients (102 clubfeet) treated by TATT for clubfoot relapses after successful initial treatment by the Ponseti method. Ten patients (15 clubfeet) experienced a subsequent relapse. Demographic, clinical, and treatment data was recorded. Results: These patients had a tendency toward a greater number of casts at initial treatment (P=0.14) and they underwent relapse surgery earlier than those who did not relapse after TATT (P=0.05). Two of these patients had a neuromyopathy, diagnosed by muscle biopsy. The treatment of post-TATT relapse included casting (6 patients), ankle foot orthotic (4 patients), physical therapy (2 patients), or bracing (1 patient). One patient was treated by osteotomies of the cuboid and medial cuneiform and 1 patient had a peroneus longus to peroneus brevis tendon transfer. Conclusions: Performing a TATT may not be the definitive treatment for clubfoot relapses as neuromuscular deficits may be involved. In addition, these patients may be at an increased risk of relapse due to the earlier age at which TATT was performed. When there is a high index of suspicion, prompt diagnosis with muscle biopsy is warranted. Level of Evidence: Level III (Case-control study).
Session Viewer: Visual Exploratory Analysis of Web Session Logs

Large-scale session log analysis typically includes statistical methods and detailed log examinations. While both methods have merits, statistical methods can miss previously unknown sub- populations in the data and detailed analyses may have selection biases. We therefore built Session Viewer, a visualization tool to facilitate and bridge between statistical and detailed analyses. Taking a multiple-coordinated view approach, Session Viewer shows multiple session populations at the Aggregate, Multiple, and Detail data levels to support different analysis styles. To bridge between the statistical and the detailed analysis levels, Session Viewer provides fluid traversal between data levels and side-by-side comparison at all data levels. We describe an analysis of a large-scale web usage study to demonstrate the use of Session Viewer, where we quantified the importance of grouping sessions based on task type.
Intact signaling by transforming growth factor β is not required for termination of liver regeneration in mice

Transforming growth factor β (TGF‐β) is a potent inhibitor of hepatocyte proliferation in vitro and is suggested to be a key negative regulator of liver growth. To directly address the role of TGF‐β signaling in liver regeneration in vivo, the TGF‐β type II receptor gene (Tgfbr2) was selectively deleted in hepatocytes by crossing “floxed” Tgfbr2 conditional knockout mice with transgenic mice expressing Cre under control of the albumin promoter. Hepatocytes isolated from liver‐specific Tgfbr2 knockout (R2LivKO) mice were refractory to the growth inhibitory effects of TGF‐β1. The peak of DNA synthesis after 70% partial hepatectomy occurred earlier (36 vs. 48 hours) and was 1.7‐fold higher in R2LivKO mice compared with controls. Accelerated S‐phase entry by proliferating R2LivKO hepatocytes coincided with the hyperphosphorylation of Rb protein and the early upregulation of cyclin D1 and cyclin E. However, by 120 hours after partial hepatectomy, hepatocyte proliferation was back to baseline in both control and R2LivKO liver. Regenerating R2LivKO liver showed evidence of increased signaling by activin A and persistent activity of the Smad pathway. Blockage of activin A signaling by the specific inhibitor follistatin resulted in increased hepatocyte proliferation at 120 hours, particularly in R2LivKO livers. In conclusion, TGF‐β regulates G1 to S phase transition of hepatocytes, but intact signaling by TGF‐β is not required for termination of liver regeneration. Increased signaling by activin A may compensate to regulate liver regeneration when signaling through the TGF‐β pathway is abolished, and may be a principal factor in the termination of liver regeneration. (HEPATOLOGY 2004.)