Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Domain Interaction Regulates Secretion of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Protein*

Background: The lack of understanding of the structure-function relation of PCSK9 hinders efforts to develop small molecule inhibitors. Results: The prodomains of C-terminal domain deletion PCSK9 mutants enable secretion of prodomain deletion mutants. Conclusion: An interaction between the prodomain and C-terminal domain regulates the secretion of PCSK9. Significance: PCSK9 may be inhibited by disrupting the interaction between the prodomain and C-terminal domain. PCSK9 (proprotein convertase subtilisin/kexin type 9) has emerged as a novel therapeutic target for hypercholesterolemia due to its LDL receptor (LDLR)-reducing activity. Although its structure has been solved, the lack of a detailed understanding of the structure-function relation hinders efforts to develop small molecule inhibitors. In this study, we used mutagenesis and transfection approaches to investigate the roles of the prodomain (PD) and the C-terminal domain (CD) and its modules (CM1–3) in the secretion and function of PCSK9. Deletion of PD residues 31–40, 41–50, or 51–60 did not affect the self-cleavage, secretion, or LDLR-degrading activity of PCSK9, whereas deletion of residues 61–70 abolished all of these functions. Deletion of the entire CD protein did not impair PCSK9 self-cleavage or secretion but completely abolished LDLR-degrading activity. Deletion of any one or two of the CD modules did not affect self-cleavage but influenced secretion and LDLR-reducing activity. Furthermore, in cotransfection experiments, a secretion-defective PD deletion mutant (ΔPD) was efficiently secreted in the presence of CD deletion mutants. This was due to the transfer of PD from the cotransfected CD mutants to the ΔPD mutant. Finally, we found that a discrete CD protein fragment competed with full-length PCSK9 for binding to LDLR in vitro and attenuated PCSK9-mediated hypercholesterolemia in mice. These results show a previously unrecognized domain interaction as a critical determinant in PCSK9 secretion and function. This knowledge should fuel efforts to develop novel approaches to PCSK9 inhibition.
Anti-Proliferative Effect of an Aqueous Extract of Prunella vulgaris in Vascular Smooth Muscle Cells

The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenic factor of vascular disorders such as diabetic atherosclerosis. We have reported the anti-inflammatory effect of an aqueous extract from Prunella vulgaris (APV) in vascular endothelial cell. In the present study, APV exhibited inhibitory effects on high glucose-stimulated VSMC proliferation, migration, and invasion activities, inducing G1 cell cycle arrest with downregulation of cyclins and CDKs and upregulation of the CKIs, p21waf1/cip1 and p27kip1. Furthermore, APV dose dependently suppressed the high glucose-induced matrix metalloproteinase activity. High glucose-induced phosphorylation of ERK, p38 MAPK, was decreased by the pretreatment of APV. NF-κB activation by high glucose was attenuated by APV, as an antioxidant. APV attenuated the high glucose-induced decrease of nuclear factor E2-related factor-2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression. Intracellular cGMP level was also increased by APV treatment. These results demonstrate that APV may inhibit VSMC proliferation via downregulating ROS/NF-κB /ERK/p38 MAPK pathways. In addition, APV has a beneficial effect by the interaction of Nrf2-mediated NO/cGMP with HO-1, suggesting that Prunella vulgaris may be useful in preventing diabetic atherosclerosis.
Switch-mode amplifier ICs with over 90% efficiency for Class-S PAs using GaAs-HBTs and GaN-HEMTs

This paper reports on design and realization of monolithic switch-mode amplifiers for data rates up to 1.8 Gbps, suitable for Class-S and inverse class-D PA modules. GaN HEMT as well as high-voltage GaAs-HBT technologies are employed and compared. For digital signal transmission without output filtering, the chips achieve efficiencies of more than 90 % at an output power of 5.4 W and 6.5 W with PAE values including the on-chip drivers, of 75% and 80% for GaAs-HBT and GaN-HEMT Ics respectively. These high efficiencies values are very promising since such PA chips represent the key building block for future class S systems.
Genetic Abnormalities in Chronic Lymphocytic Leukemia: Where We Are and Where We Go

Chromosomal abnormalities in chronic lymphocytic leukemia (CLL) are detected in up to 80% of patients. Among them, deletions of 11q, 13q, 17p, and trisomy 12 have a known prognostic value and play an important role in CLL pathogenesis and evolution, determining patients outcome and therapeutic strategies. Standard methods used to identify these genomic aberrations include both conventional G-banding cytogenetics (CGC) and fluorescence in situ hybridization (FISH). Although FISH analyses have been implemented as the gold standard, CGC allows the identification of chromosomal translocations and complex karyotypes, the latest associated with poor outcome. Genomic arrays have a higher resolution that allows the detection of cryptic abnormalities, although these have not been fully implemented in routine laboratories. In the last years, next generation sequencing (NGS) methods have identified a wide range of gene mutations (e.g., TP53, NOTCH1, SF3B1, and BIRC3) which have improved our knowledge about CLL development, allowing us to refine both the prognostic subgroups and better therapeutic strategies. Clonal evolution has also recently arisen as a key point in CLL, integrating cytogenetic alterations and mutations in a dynamic model that improve our understanding about its clinical course and relapse.
A Multilingual Database of Idioms

This paper presents a possible architecture for a multilingual database of idioms. We discuss the challenges that idioms present to the creation of such a database and propose a possible encoding that maximises the amount of information that can be stored for different languages. Such a resource provides important information for linguistic, computational linguistic and psycholinguistic use, and allows for the comparison of different phenomena in different languages. This can provide the basis for a better understanding of regularities in idioms across languages.
Linear structures following by an airship using vanishing point and horizon line in a visual servoing scheme

In the present paper, an image-based visual servoing scheme is presented for a road following task with an autonomous airship. A new set of visual signals is introduced, namely with the vanishing point coordinates and the vanishing line parameters, which have the advantage of decoupling the rotation DOF and respecting the natural characteristics of the vehicle dynamics. An optimal control design is used for a first implementation of the approach with the simulation platform of the AURORA airship. Simulation results are presented and discussed demonstrating a fair performance even in realistic wind conditions.
A 6.6-kV Transformerless Motor Drive Using a Five-Level Diode-Clamped PWM Inverter for Energy Savings of Pumps and Blowers

This paper describes a 6.6-kV adjustable-speed motor drive for pumps and blowers without transformer. The power conversion system consists of a front-end diode rectifier, a five-level diode-clamped pulsewidth modulation (PWM) inverter with a voltage balancing circuit, and a hybrid active filter for harmonic-current mitigation of the diode rectifier. The control of the inverter is characterized by superimposing a third-harmonic zero-sequence voltage on each of the three-phase reference voltages to achieve the so-called overmodulation and reduce the switching stress of insulated gate bipolar transistors (IGBTs). A 200-V 5.5-kW downscale model is designed, constructed, and tested with focus on the five-level PWM inverter and the voltage balancing circuit. Experimental results obtained from the 200-V downscale model verify the viability and effectiveness of the 6.6-kV adjustable-speed motor drive, showing that the four split dc capacitor voltages are well balanced in all the operating conditions and that the switching stress of the IGBTs is reduced at low modulation indexes.
Probabilistic Analysis of Low-Criticality Execution

The mixed-criticality toolbox promises system architects a powerful framework for consolidating real-time tasks with different safety properties on a single computing platform. Thanks to the research efforts in the mixed-criticality field, guarantees provided to the highest criticality level are well understood. However, lower-criticality job execution depends on the condition that all high-criticality jobs complete within their more optimistic low-criticality execution time bounds. Otherwise, no guarantees are made. In this paper, we add to the mixed-criticality toolbox by providing a probabilistic analysis method for low-criticality tasks. While deterministic models reduce task behavior to constant numbers, probabilistic analysis captures varying runtime behavior. We introduce a novel algorithmic approach for probabilistic timing analysis, which we call symbolic scheduling. For restricted task sets, we also present an analytical solution. We use this method to calculate per-job success probabilities for low-criticality tasks, in order to quantify, how low-criticality tasks behave in case of high-criticality jobs overrunning their optimistic low-criticality reservation.
Genes Required for the Anti-fungal Activity of a Bacterial Endophyte Isolated from a Corn Landrace Grown Continuously by Subsistence Farmers Since 1000 BC

Endophytes are microbes that inhabit internal plant tissues without causing disease. Some endophytes are known to combat pathogens. The corn (maize) landrace Chapalote has been grown continuously by subsistence farmers in the Americas since 1000 BC, without the use of fungicides, and the crop remains highly valued by farmers, in part for its natural tolerance to pests. We hypothesized that the pathogen tolerance of Chapalote may, in part, be due to assistance from its endophytes. We previously identified a bacterial endophyte from Chapalote seeds, Burkholderia gladioli strain 3A12, for its ability to combat a diversity of crop pathogens, including Sclerotinia homoeocarpa, the most important fungal disease of creeping bentgrass, a relative of maize used here as a model system. Strain 3A12 represents a unique opportunity to understand the anti-fungal activities of an endophyte associated with a crop variety grown by subsistence farmers since ancient times. Here, microscopy combined with Tn5-mutagenesis demonstrates that the anti-fungal mode of action of 3A12 involves flagella-dependent swarming toward its pathogen target, attachment and biofilm-mediated microcolony formation. The mutant screen revealed that YajQ, a receptor for the secondary messenger c-di-GMP, is a critical signaling system that mediates this endophytic mobility-based defense for its host. Microbes from the traditional seeds of farmers may represent a new frontier in elucidating host–microbe mutualistic interactions.
Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis

Background Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice. Methods We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]). Conclusions There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.
Effectiveness of Standardized Nursing Care Plans in Health Outcomes in Patients with Type 2 Diabetes Mellitus: A Two-Year Prospective Follow-Up Study

Background Implementation of a standardized language in Nursing Care Plans (SNCP) allows for increased efficiency in nursing data management. However, the potential relationship with patientś health outcomes remains uncertain. The aim of this study was to evaluate the effectiveness of SNCP implementation, based on North American Nursing Diagnosis Association (NANDA) and Nursing Interventions Classification (NIC), in the improvement of metabolic, weight, and blood pressure control of Type 2 Diabetes Mellitus (T2DM) patients. Methods A two-year prospective follow-up study, in routine clinical practice conditions. 31 primary health care centers (Spain) participated with 24,124 T2DM outpatients. Data was collected from Computerized Clinical Records; SNCP were identified using NANDA and NIC taxonomies. Descriptive and ANCOVA analyses were conducted. Results 18,320 patients were identified in the Usual Nursing Care (UNC) group and 5,168 in the SNCP group. At the two-year follow-up, the SNCP group improved all parameters except LDL cholesterol and diastolic blood pressure. We analyzed data adjustming by the baseline value for these variables and variables with statistically significant differences between groups at baseline visit. Results indicated a lowering of all parameters except HbA1c, but a statistically significant reduction was only observed with diastolic blood pressure results. However, the adjusted reduction of diastolic blood pressure is of little clinical relevance. Greater differences of control values for diastolic blood pressure, HbA1c, LDL-cholesterol and Body Mass Index were found in the SNCP group, but only reached statistical significance for HbA1c. A greater proportion of patients with baseline HbA1c ≥7 decreased to <7% at the two-year follow-up in the SNCP group than in the UNC group (16.9% vs. 15%; respectively; p = 0.01). Conclusions Utilization of SNCP was helpful in achieving glycemic control targets in poorly controlled patients with T2DM (HbA1c ≥7%). Diastolic blood pressure results were slightly improved in the SNCP group compared to the UNC group. Trial Registration ClinicalTrials.gov NCT01482481
Rigorous Design and Optimization of Brushless PM Motor Using Response Surface Methodology with Quantum-Behaved PSO Operator

In this paper, a rigorous design of a brushless permanent-magnet (PM) motor with both lower cogging torque and higher efficiency, using response surface methodology (RSM) with a quantum-behaved PSO (QPSO) operator for a portable electric power drill application, has been presented. To decrease noise and vibration of a slotted PM motor, cogging torque must be reduced. Some skew techniques have obvious advantages of reducing cogging torque. In particular, the stepped equivalent model with its cost-effectiveness can be employed to design a high-performance PM motor for portable electric power drills in this paper. To find the most suitable combination of the geometric parameters of a brushless PM motor with skewed magnets to achieve the design goal, the RSM with a QPSO operator is employed. The 3-D finite element method (FEM) is employed as the tool for analyzing the cogging torque and performance of the proposed PM motor. The experimental results show that the proposed method can obtain the best combination of the geometric parameters for reducing the cogging torque and enhancing the operating efficiency.
Study of Robust Distributed Beamforming Based on Cross-Correlation and Subspace Projection Techniques

In this work, we present a novel robust distributed beamforming (RDB) approach to mitigate the effects of channel errors on wireless networks equipped with relays based on the exploitation of the cross-correlation between the received data from the relays at the destination and the system output. The proposed RDB method, denoted cross-correlation and subspace projection (CCSP) RDB, considers a total relay transmit power constraint in the system and the objective of maximizing the output signal-to-interference-plus-noise ratio (SINR). The relay nodes are equipped with an amplify-and-forward (AF) protocol and we assume that the channel state information (CSI) is imperfectly known at the relays and there is no direct link between the sources and the destination. The CCSP does not require any costly optimization procedure and simulations show an excellent performance as compared to previously reported algorithms.
An essential RNA element resides in a central region of hepatitis E virus ORF2

Hepatitis E virus (genus Hepevirus, family Hepeviridae) is one of the most important causes of acute hepatitis in adults, particularly among pregnant women, throughout Asia and Africa where mortality rates can be 20–30 %. Hepatitis E virus has a single-stranded positive-sense RNA genome that contains three translated ORFs. The two 3′ ORFs are translated from a subgenomic RNA. Functional RNA elements have been identified in and adjacent to the genomic 5′ and 3′ UTRs and in and around the intergenic region. Here we describe an additional RNA element that is located in a central region of ORF2. The RNA element is predicted to fold into two highly conserved stem–loop structures, ISL1 and ISL2. Mutations that disrupt the predicted structures, without altering the encoded amino acid sequence, result in a drastic reduction in capsid protein synthesis. This indicates that the RNA element plays an important role in one of the early steps of virus replication. The structures were further investigated using a replicon that expresses Gaussia luciferase in place of the capsid protein. Single mutations in ISL2 severely reduced luciferase expression, but a pair of compensatory mutations that were predicted to restore the ISL2 structure, restored luciferase expression to near-WT levels, thus lending experimental support to the predicted structure. Nonetheless the precise role of the ISL1+ISL2 element remains unknown.
Loss in connectivity among regions of the brain reward system in alcohol dependence

A recently developed measure of structural brain connectivity disruption, the loss in connectivity (LoCo), is adapted for studies in alcohol dependence. LoCo uses independent tractography information from young healthy controls to project the location of white matter (WM) microstructure abnormalities in alcohol‐dependent versus nondependent individuals onto connected gray matter (GM) regions. LoCo scores are computed from WM abnormality masks derived at two levels: (1) groupwise differences of alcohol‐dependent individuals (ALC) versus light‐drinking (LD) controls and (2) differences of each ALC individual versus the LD control group. LoCo scores based on groupwise WM differences show that GM regions belonging to the extended brain reward system (BRS) network have significantly higher LoCo (i.e., disconnectivity) than those not in this network (t = 2.18, P = 0.016). LoCo scores based on individuals' WM differences are also higher in BRS versus non‐BRS (t = 5.26, P = 3.92 × 10−6) of ALC. These results suggest that WM alterations in alcohol dependence, although subtle and spatially heterogeneous across the population, are nonetheless preferentially localized to the BRS. LoCo is shown to provide a more sensitive estimate of GM involvement than conventional volumetric GM measures by better differentiating between brains of ALC and LD controls (rates of 89.3% vs. 69.6%). However, just as volumetric measures, LoCo is not significantly correlated with standard metrics of drinking severity. LoCo is a sensitive WM measure of regional cortical disconnectivity that uniquely characterizes anatomical network disruptions in alcohol dependence. Hum Brain Mapp 34:3129–3142, 2013. © 2012 Wiley Periodicals, Inc.
Recommending Web Services via Combining Collaborative Filtering with Content-Based Features

With increasing adoption and presence of Web services, designing novel approaches for efficient Web services recommendation has become steadily more important. Existing Web services discovery and recommendation approaches focus on either perishing UDDI registries, or keyword-dominant Web service search engines, which possess many limitations such as insufficient recommendation performance and heavy dependence on the input from users such as preparing complicated queries. In this paper, we propose a novel approach that dynamically recommends Web services that fit users' interests. Our approach is a hybrid one in the sense that it combines collaborative filtering and content-based recommendation. In particular, our approach considers simultaneously both rating data and content data of Web services using a three-way aspect model. Unobservable user preferences are represented by introducing a set of latent variables, which is statistically estimated. To verify the proposed approach, we conduct experiments using 3, 693 real-world Web services. The experimental results show that our approach outperforms the two conventional methods on recommendation performance.
Scalable Action Respecting Embedding

ARE is a non-linear dimensionality reduction technique for embedding observation trajectories, which captures state dynamics that traditional methods do not. The core of ARE is a semidefinite optimization with constraints requiring actions to be distance-preserving in the resulting embedding. Unfortunately, these constraints are quadratic in number and non-local (making recent scaling tricks inapplicable). Consequently, the original formulation was limited to relatively small datasets. This paper describes two techniques to mitigate these issues. We first introduce an action-guided variant of Isomap. Although it alone does not produce actionrespecting manifolds, it can be used to seed conjugate gradient to implicitly solve the primal variable formulation of the ARE optimization. The optimization is not convex, but the Action-Guided Isomap provides an excellent seed often very close to the global minimum. The resulting Scalable ARE procedure gives similar results to original ARE, but can be applied to datasets an order of magnitude larger.