Miracle-dz/UniFAR-FTUs huggingface dataset:
Globally Asymptotic Stability of a Class of Neutral-Type Neural Networks With Delays

Several stability conditions for a class of systems with retarded-type delays are presented in the literature. However, no results have yet been presented for neural networks with neutral-type delays. Accordingly, this correspondence investigates the globally asymptotic stability of a class of neutral-type neural networks with delays. This class of systems includes Hopfield neural networks, cellular neural networks, and Cohen-Grossberg neural networks. Based on the Lyapunov stability method, two delay-independent sufficient stability conditions are derived. These stability conditions are easily checked and can be derived from the connection matrix and the network parameters without the requirement for any assumptions regarding the symmetry of the interconnections. Two illustrative examples are presented to demonstrate the validity of the proposed stability criteria
Essential and redundant functions of histone acetylation revealed by mutation of target lysines and loss of the Gcn5p acetyltransferase

The Gcn5p histone acetyltransferase exhibits a limited substrate specificity in vitro. However, neither the specificity of this enzyme in vivo nor the importance of particular acetylated residues to transcription or cell growth are well defined. To probe these questions, we mutated specific lysines in the N‐termini of histones H3 and H4 and examined the effects of these mutations in yeast strains with and without functional GCN5. We found that in vivo, GCN5 is required either directly or indirectly for the acetylation of several sites in H3 and H4 in addition to those recognized by the recombinant enzyme in vitro. Moreover, in the absence of GCN5, cells accumulate in G2/M indicating that Gcn5p functions are important for normal cell‐cycle progression. Mutation of K14 in H3, which serves as the major target of recombinant Gcn5p acetylation in vitro, confers a strong, synthetic growth defect in gcn5 cells. Synergistic growth defects were also observed in gcn5 cells carrying mutations in lysine pairs (K8/K16 or K5/K12) in histone H4. Strikingly, simultaneous mutation of K14 in H3 and K8 and K16 in H4 to arginine, or deletion of either the H3 or the H4 N‐terminal tail, results in the death of gcn5 cells. Mutation of these same three sites to glutamine is not lethal. Indeed, this combination of mutations largely bypasses the need for GCN5 for transcriptional activation by Gal4–VP16, supporting an important role for histone acetylation in Gcn5p‐mediated regulation of transcription. Our data indicate that acetylation of particular lysines in histones H3 and H4 serves both unique and overlapping functions important for normal cell growth, and that a critical overall level of histone acetylation is essential for cell viability.
Trimming Down a Protein Structure to Its Bare Foldons

Background: Structural cooperativity safeguards native proteins but is yet poorly understood. Results: Guided by the folding nucleus, we reduced the size of a protein without compromising its structural integrity. Conclusion: Folding nuclei are used in a modular fashion to extend or reduce the cooperative units of proteins. Significance: Understanding cooperativity is crucial for understanding protein function and for rational design of structural properties. Folding of the ribosomal protein S6 is a malleable process controlled by two competing, and partly overlapping, folding nuclei. Together, these nuclei extend over most of the S6 structure, except the edge strand β2, which is consistently missing in the folding transition states; despite being part of the S6 four-stranded sheet, β2 seems not to be part of the cooperative unit of the protein. The question is then whether β2 can be removed from the S6 structure without compromising folding cooperativity or native state integrity. To investigate this, we constructed a truncated variant of S6 lacking β2, reducing the size of the protein from 96 to 76 residues (S6Δβ2). The new S6 variant expresses well in Escherichia coli and has a well dispersed heteronuclear single quantum correlation spectrum and a perfectly wild-type-like crystal structure, but with a smaller three-stranded β-sheet. Moreover, S6Δβ2 displays an archetypical v-shaped chevron plot with decreased slope of the unfolding limb, as expected from a protein with maintained folding cooperativity and reduced size. The results support the notion that foldons, as defined by the structural distribution of the folding nuclei, represent a property-based level of hierarchy in the build-up of larger protein structures and suggest that the role of β2 in S6 is mainly in intermolecular binding, consistent with the position of this strand in the ribosomal assembly.
Single-DC-source five-level CHB inverter with sensor-less voltage balancing

A single-dc-source 5-level cascaded H-bridge (CHB) inverter is studied in this paper. All possible switching sequences are analyzed and a sensor-less voltage balancing approach is proposed that regulates the second dc bus (capacitor) voltage at half of the first dc bus amplitude (isolated dc source). The output voltage levels include zero, capacitor voltage and the dc source amplitude. The simple sensor-less voltage balancing technique is integrated into switching method which makes it easy to implement using even cheap microcontrollers. Simulation results validate the good dynamic performance of the proposed sensor-less voltage controller in regulating the capacitor voltage at the desired level to generate 5-level asymmetric voltage waveform at the inverter output low harmonics contents.
12. Collective Agreements and Equal Opportunities for Women and Disadvantaged Groups

This contribution researches the impact of collective agreements on female management and job opportunities of employees from disadvantaged groups (including migrants or their descendants) in 4053 enterprises in Europe. Graafland f inds that collective agreements stimulate female presence in board and executive positions, and the inflow of employees from disadvantaged groups (e.g. migrant workers, people with disabilities, long-term unemployed). Moreover, female management further enforces job opportunities of disadvantaged workers. Countries with high coverage of collective agreements therefore, directly as well as indirectly, through female management, foster integration of employees from disadvantaged groups into the labour market. The results imply that dismantling extensions of collective agreements in the labour market increases gender inequality and inequality between advantaged and disadvantaged groups of employees.
Gamma Knife treatment planning: MR brain tumor segmentation and volume measurement based on unsupervised Fuzzy C‐Means clustering

Nowadays, radiation treatment is beginning to intensively use MRI thanks to its greater ability to discriminate healthy and diseased soft‐tissues. Leksell Gamma Knife® is a radio‐surgical device, used to treat different brain lesions, which are often inaccessible for conventional surgery, such as benign or malignant tumors. Currently, the target to be treated with radiation therapy is contoured with slice‐by‐slice manual segmentation on MR datasets. This approach makes the segmentation procedure time consuming and operator‐dependent. The repeatability of the tumor boundary delineation may be ensured only by using automatic or semiautomatic methods, supporting clinicians in the treatment planning phase. This article proposes a semiautomatic segmentation method, based on the unsupervised Fuzzy C‐Means clustering algorithm. Our approach helps segment the target and automatically calculates the lesion volume. To evaluate the performance of the proposed approach, segmentation tests on 15 MR datasets were performed, using both area‐based and distance‐based metrics, obtaining the following average values: Similarity Index = 95.59%, Jaccard Index = 91.86%, Sensitivity = 97.39%, Specificity = 94.30%, Mean Absolute Distance = 0.246[pixels], Maximum Distance = 1.050[pixels], and Hausdorff Distance = 1.365[pixels]. © 2015 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 25, 213–225, 2015
Computerized Summative Assessment of Multiple-choice Questions: Exploring Possibilities with the Zimbabwe School Examination Council Grade 7 Assessments

The purpose of this study was to develop educational software for online assessment of multiple choice responses (MCQs). An automated assessment software program, duly developed in this study can display assessment items, record candidates' answers, and mark and provide instant reporting of candidates' performance scores. Field tests of the software were conducted on four primary schools located in Bindura town using a previous year summative Grade 7 assessment set by the Zimbabwe School Examination Council (ZIMSEC). Results were that computerized assessment in mathematics has the potential to enhance the quality of assessment standards and can drastically reduce material costs to the examination board. The paper exposes test mode benefits inherent in computer-based assessments, such as one-item display and ease of candidates selecting/changing optional answers. It also informs the ongoing debate on possible enhancement of candidates' performance on a computer-based assessment relative to the traditional pen-and-paper assessment format. The need for the development of diagnostic instructional software to compliment computerized assessments is one of the recommendations of the study.
Pharmacokinetics and pharmacodynamics in antibiotic dose optimization

Introduction: Identifying the optimized dosing regimen and algorithm is critical in the development of antibiotics. Suboptimal regimens and inappropriate choice of drug give rise to drug-resistant bacteria which have limited the therapeutic utility of many commercially available antimicrobial agents. Strategies to optimize therapy of antimicrobial candidates to speed up the development process are urgently needed. Areas covered: We examined pharmacokinetics and pharmacodynamics of antimicrobial agents with modeling and simulation approaches. The approach that is based on minimum inhibitory concentration to evaluate antimicrobial dosing strategy is widely utilized in drug development. The modeling approach utilizing information from time-kill kinetic studies is a tool that can provide more information on the time-course of bacterial response to a particular dosing regimen. Animal studies of dosing regimens that mimic human pharmacokinetics are another option to evaluate antimicrobial efficacy. Empirical, semi-mechanistic and mechanistic models of bacterial dynamics and development of drug resistance in response to drug therapy are discussed. Expert opinion: Both theories and applications of these approaches provide an overall understanding of how the tools can streamline drug development process and help make crucial decisions. Many opportunities and potentials are presented to incorporate more rigorous integration of PK-PD modeling approaches even at preclinical stage to extrapolate to clinical settings, thus enabling successful trials and optimizing dosing strategies in relevant populations where the drug is mostly used.
Traumatic fibrotic myopathy of the tensor fascia lata muscle in a Whippet

Summary A two-year-old female neutered Whippet was referred for evaluation of progressive right pelvic limb lameness. Clinical examination revealed a fibrous band palpable along the cranial aspect of the quadriceps muscle group, and signs of discomfort on extension of the right hip. Computed tomography and ultrasonographic examination revealed mineralization of the tensor fascia lata muscle with enthesophytosis of its origin. Surgical exploration confirmed a fibrous band affecting the cranial border of the tensor fascia lata muscle. Resection of the band resulted in complete resolution of clinical signs. Histopathology was consistent with a fibrotic myopathy. To the authors’ knowledge, this is the first case of a fibrotic myopathy affecting the tensor fascia lata muscle in the dog.
Accomplishing being ordinary : identity talk of people conditionally-discharged from secure forensic settings

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CALIPSO/CALIOP Cloud Phase Discrimination Algorithm

Abstract The current cloud thermodynamic phase discrimination by Cloud-Aerosol Lidar Pathfinder Satellite Observations (CALIPSO) is based on the depolarization of backscattered light measured by its lidar [Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP)]. It assumes that backscattered light from ice crystals is depolarizing, whereas water clouds, being spherical, result in minimal depolarization. However, because of the relationship between the CALIOP field of view (FOV) and the large distance between the satellite and clouds and because of the frequent presence of oriented ice crystals, there is often a weak correlation between measured depolarization and phase, which thereby creates significant uncertainties in the current CALIOP phase retrieval. For water clouds, the CALIOP-measured depolarization can be large because of multiple scattering, whereas horizontally oriented ice particles depolarize only weakly and behave similarly to water clouds. Because of the nonunique depolarization–cloud ph.
Defining Benchmarks for Major Liver Surgery: A multicenter Analysis of 5202 Living Liver Donors

Objective: To measure and define the best achievable outcome after major hepatectomy. Background: No reference values are available on outcomes after major hepatectomies. Analysis in living liver donors, with safety as the highest priority, offers the opportunity to define outcome benchmarks as the best possible results. Methods: Outcome analyses of 5202 hemi-hepatectomies from living donors (LDs) from 12 high-volume centers worldwide were performed for a 10-year period. Endpoints, calculated at discharge, 3 and 6 months postoperatively, included postoperative morbidity measured by the Clavien-Dindo classification, the Comprehensive Complication Index (CCI), and liver failure according to different definitions. Benchmark values were defined as the 75th percentile of median morbidity values to represent the best achievable results at 3 month postoperatively. Results: Patients were young (34 ± [9] years), predominantly male (65%) and healthy. Surgery lasted 7 ± [2] hours; 2% needed blood transfusions. Mean hospital stay was 11.7± [5] days. 12% of patients developed at least 1 complication, of which 3.8% were major events (≥grade III, including 1 death), mostly related to biliary/bleeding events, and were twice higher after right hepatectomy. The incidence of postoperative liver failure was low. Within 3-month follow-up, benchmark values for overall complication were ⩽31 %, for minor/major complications ⩽23% and ⩽9%, respectively, and a CCI ⩽33 in LDs with complications. Centers having performed ≥100 hepatectomies had significantly lower rates for overall (10.2% vs 35.9%, P < 0.001) and major (3% vs 12.1%, P < 0.001) complications and overall CCI (2.1 vs 8.5, P < 0.001). Conclusions: The thorough outcome analysis of healthy LDs may serve as a reference for evaluating surgical performance in patients undergoing major liver resection across centers and different patient populations. Further benchmark studies are needed to develop risk-adjusted comparisons of surgical outcomes.
Non-uniqueness in time-optimal control of robotic manipulators

For serially-actuated open-chain robotic manipulators, the existence of non-unique extremals for the state-to-state time-optimal control problem is established. Non-uniqueness is shown to arise through infinite order singular extremals, the properties of which depend on the coupling that is present in the manipulator. Furthermore, it is demonstrated using counter-examples, that infinite order singularity does not necessarily occur, when the actuation is not serial or when the manipulator has a closed chain structure.
The Potyviral P3 Protein Targets Eukaryotic Elongation Factor 1A to Promote the Unfolded Protein Response and Viral Pathogenesis1[OPEN]

Soybean Mosaic Virus P3 targets soybean elongation factor EF1A to induce ER stress, which in turn facilitates SMV pathogenesis and this is linked to EF1A function in translation elongation. The biochemical function of the potyviral P3 protein is not known, although it is known to regulate virus replication, movement, and pathogenesis. We show that P3, the putative virulence determinant of soybean mosaic virus (SMV), targets a component of the translation elongation complex in soybean. Eukaryotic elongation factor 1A (eEF1A), a well-known host factor in viral pathogenesis, is essential for SMV virulence and the associated unfolded protein response (UPR). Silencing GmEF1A inhibits accumulation of SMV and another ER-associated virus in soybean. Conversely, endoplasmic reticulum (ER) stress-inducing chemicals promote SMV accumulation in wild-type, but not GmEF1A-knockdown, plants. Knockdown of genes encoding the eEF1B isoform, which is important for eEF1A function in translation elongation, has similar effects on UPR and SMV resistance, suggesting a link to translation elongation. P3 and GmEF1A promote each other’s nuclear localization, similar to the nuclear-cytoplasmic transport of eEF1A by the Human immunodeficiency virus 1 Nef protein. Our results suggest that P3 targets host elongation factors resulting in UPR, which in turn facilitates SMV replication and place eEF1A upstream of BiP in the ER stress response during pathogen infection.
Interferon-γ Potentiates Interleukin (IL)-6 and Tumor Necrosis Factor-α But Not IL-1β Induced by Endotoxin in the Brain.

Because interferon-γ (IFNγ) is present in the central nervous system during neurologic diseases associated with inflammation, its effect on endotoxin-induced cytokines was studied. Cerebrospinal fluid (CSF) and serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNFα), their messenger RNA expression in brain areas (hypothalamus, hyppocampus, and striatum) and in spleen were evaluated 2 and 8 h after endotoxin [lipopolysaccharide (LPS), 25μ g/rat icv], IFNγ (2.5 μg/rat icv) or after their coadministration in rats. CSF and serum IL-1β levels were increased by LPS alone and IFNγ coadministration did not furtherly increase them. IFNγ potentiated LPS effect on IL-6 and TNFα levels in both CSF and serum. LPS and IFN-γ coadministration did not alter IL-1β messenger RNA expression induced by LPS in brain areas and in spleen, but it potentiated that of IL-6 and TNFα. The present in vivo data show that icv coadministration of LPS and IFNγ results in a potentiation of cytokine production (IL-6 an.
Unravelling the biology of chromatin in health and cancer using proteomic approaches

ABSTRACT Introduction: Chromatin remodeling complexes play important roles in the control of genome regulation in both normal and diseased states, and are therefore critical components for the regulation of epigenetic states in cells. Given the role epigenetics plays in cancer, for example, chromatin remodeling complexes are routinely targeted for therapeutic intervention. Areas covered: Protein mass spectrometry and proteomics are powerful technologies used to study and understand chromatin remodeling. While impressive progress has been made in this area, there remain significant challenges in the application of proteomic technologies to the study of chromatin remodeling. As parts of large multi-subunit complexes that can be heavily modified with dynamic post-translational modifications, challenges in the study of chromatin remodeling complexes include defining the content, determining the regulation, and studying the dynamics of the complexes under different cellular states. Expert commentary: Impwortant considerations in the study of chromatin remodeling complexes include the complexity of sample preparation, the choice of proteomic methods for the analysis of samples, and data analysis challenges. Continued research in these three areas promise to yield even greater insights into the biology of chromatin remodeling and epigenetics and the dynamics of these systems in human health and cancer.
Primary intestinal lymphangiectasia treated with rapamycin in a child with tuberous sclerosis complex (TSC)

Primary intestinal lymphangiectasia (PIL) is a rare protein‐losing enteropathy characterized by a congenital malformation of the lymphatic vessels of the small intestine causing insufficient drainage and leakage of lymph fluid. Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems. While the lymphatic system has been implicated in TSC through lymphangioleiomyomatosis (LAM) and lymphedema, this paper reports the first case of PIL in TSC, a female patient with a TSC2 mutation. She developed persistent and significant abdominal distension with chronic diarrhea during her first year of life. Due to lack of treatment options and the involvement of the mTOR pathway in TSC, a trial of an mTOR inhibitor, rapamycin, was initiated. This treatment was highly effective, with improvement in clinical symptoms of PIL as well as abnormal laboratory values including VEGF‐C, which was elevated to over seven times the normal upper limit before treatment. This case suggests that PIL is a rare manifestation of TSC, warranting the use of mTOR inhibitors in future studies. © 2015 Wiley Periodicals, Inc.
IRE‐1/XBP‐1 pathway of the unfolded protein response is required for properly localizing neuronal UNC‐6/Netrin for axon guidance in C. elegans

During developing nervous system, neurons project axons to their targets precisely. In this process, axon guidance molecules provide positional information to the axons. Therefore, the spatially and temporally controlled localization of the axon guidance molecules is required for the proper structure formation of the complex nervous system. In C. elegans, UNC‐6/Netrin is a secreted protein that elicits both attractive and repulsive response in axon guidance. UNC‐6/Netrin secreted from ventral cells may establish a concentration gradient from the ventral to the dorsal side of the animal, thus providing dorso‐ventral positional information. However, the mechanisms specifying positional information of UNC‐6/Netrin are largely unknown. Here, we show that the ire‐1/xbp‐1 pathway of the unfolded protein response (UPR) is required for axonal distribution of UNC‐6/Netrin in the ventral neurons. In addition, the ire‐1/xbp‐1 pathway is also required for dorso‐ventral axon guidance mediated by UNC‐6/Netrin. Our results suggest that the ire‐1/xbp‐1 pathway of the UPR is crucial for establishing positional information of UNC‐6/Netrin. We propose that the proper secretion of UNC‐6/Netrin from the ventral neurons requires the activity of IRE‐1.