Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidermal Growth Factor (EGF) Ligand Release by Substrate-specific A Disintegrin and Metalloproteases (ADAMs) Involves Different Protein Kinase C (PKC) Isoenzymes Depending on the Stimulus*

The dysregulation of EGF family ligand cleavage has severe consequences for the developing as well as the adult organism. Therefore, their production is highly regulated. The limiting step is the ectodomain cleavage of membrane-bound precursors by one of several a disintegrin and metalloprotease (ADAM) metalloproteases, and understanding the regulation of cleavage is an important goal of current research. We have previously reported that in mouse lung epithelial cells, the pro-EGF ligands TGFα, neuregulin 1β (NRG), and heparin-binding EGF are differentially cleaved depending on the cleavage stimulus (Herrlich, A., Klinman, E., Fu, J., Sadegh, C., and Lodish, H. (2008) FASEB J.). In this study in mouse embryonic fibroblasts that lack different ADAMs, we show that induced cleavage of EGF ligands can involve the same substrate-specific metalloprotease but does require different stimulus-dependent signaling pathways. Cleavage was stimulated by phorbol ester (12-O-tetradecanoylphorbol-13-acetate (TPA), a mimic of diacylglycerol and PKC activator), hypertonic stress, lysophosphatidic acid (LPA)-induced G protein-coupled receptor activation, or by ionomycin-induced intracellular calcium release. Although ADAMs showed substrate preference (ADAM17, TGFα and heparin-binding EGF; and ADAM9, NRG), substrate cleavage differed substantially with the stimulus, and cleavage of the same substrate depended on the presence of different, sometimes multiple, PKC isoforms. For instance, classical PKC was required for TPA-induced but not hypertonic stress-induced cleavage of all EGF family ligands. Inhibition of PKCζ enhanced NRG release upon TPA stimulation, but it blocked NRG release in response to hypertonic stress. Our results suggest a model in which substantial regulation of ectodomain cleavage occurs not only on the metalloprotease level but also on the level of the substrate or of a third protein.
Locking Regulatory Myosin in the Off-state with Trifluoperazine*

Scallop striated adductor muscle myosin is a regulatory myosin, its activity being controlled directly through calcium binding. Here, we show that millimolar concentrations of trifluoperazine were effective at removal of all regulatory light chains from scallop myosin or myofibrils. More important, 200 μm trifluoperazine, a concentration 10-fold less than that required for light-chain removal, resulted in the reversible elimination of actin-activated and intrinsic ATPase activities. Unlike desensitization induced by metal ion chelation, which leads to an elevation of activity in the absence of calcium concurrent with regulatory light-chain removal, trifluoperazine caused a decline in actin-activated MgATPase activity both in the presence and absence of calcium. Procedures were equally effective with respect to scallop myosin, myofibrils, subfragment-1, or desensitized myofibrils. Increased α-helicity could be induced in the isolated essential light chain through addition of 100–200 μm trifluoperazine. We propose that micromolar concentrations of trifluoperazine disrupt regulation by binding to a single high-affinity site located in the C-terminal domain of the essential light chain, which locks scallop myosin in a conformation resembling the off-state. At millimolar trifluoperazine concentrations, additional binding sites on both light chains would be filled, leading to regulatory light-chain displacement.
Cutting Edge: H-2DM Is Responsible for the Large Differences in Presentation Among Peptides Selected by I-Ak During Antigen Processing 1

We quantitated the amounts of peptides from hen egg-white lysozyme presented by I-Ak molecules in APC lines. The large chemical gradient of presentation of the four hen egg-white lysozyme epitopes observed in cell lines expressing HLA-DM or H-2DM (referred to in this study as DM) was significantly diminished in the T2.Ak line lacking DM. Differences in levels of presentation between wild-type and DM-deficient APC were observed for all four epitopes, but differences were most evident for the highest affinity epitope. As a result of these quantitative differences in display, presentation of all four epitopes to T cells was impaired in the line lacking DM. The binding affinity of the pool of naturally processed peptides from DM-expressing lines was higher than that from the DM-deficient line. Thus, using a direct biochemical approach in APC, we demonstrate that DM influences the selection of peptides bound to MHC class II by favoring high affinity peptides.
Assessment of bacteria and archaea in metalworking fluids using massive parallel 16S rRNA gene tag sequencing

Determination of the bacterial diversity in industry‐based liquid in‐use water‐miscible metalworking fluid (MWF) samples was targeted by massive parallel multiplex DNA sequencing, either directly or upon pretreatment with propidium monoazide (PMA) that allows differentiation between intact and physically damaged cells. As MWFs provide a suitable basis of life for micro‐organisms, the majority is preserved by biocides. ‘Bio‐concept’ fluids on the other hand are bactericide free, which intentionally leads to substantial bacterial populations. Samples from both fluid types were chosen: A median of 51 operational taxonomic units at genera level (OTUs) were detected per sample, but only 13 were present at or above 1·0% of the total population in any PMA‐treated sample analysed. As both fluid types were mainly dominated by Pseudomonas spp. , we resolved this genus on the species level and found the Pseudomonas oleovorans/pseudoalcaligenes group to predominate. We also looked for archaea and detected Methanobrevibacter spp. , albeit in <3% of all samples analysed.
Prediction of care burden of patients undergoing haemodialysis: development of a measuring tool.

BACKGROUND The ageing of the population and new options for therapy have led to an increase in the number of patients undergoing dialysis. Rising costs in health care and new financial structures impose funding constraints on dialysis departments and force the departments to deploy nurses more efficiently. Therefore, predicting the nursing time spent on the care of patients is important. OBJECTIVE Development of a classification tool to predict the burden of nursing care of patients undergoing dialysis. DESIGN Observational study. PARTICIPANTS 242 patients on dialysis in 12 centres. MEASUREMENTS The time spent on nursing care within predefined areas, including patient independence, vascular access, psychosocial support, dialysis complexity, communication and specific nursing actions, was measured by observers. Average times and their standard deviations (SD) were calculated. Variation of patient characteristics was analysed. RESULTS The average care time required for the four routine investigated domains, namely independence, vascular access, psychosocial support and dialysis complexity, was 59.23 (SD = 24.30) minutes per treatment per patient. CONCLUSION Our study shows that it is possible to predict the burden of nursing care of patients undergoing dialysis by means of a classification model.
Lusitropic effect of MCC-135 is associated with improvement of sarcoplasmic reticulum function in ventricular muscles of rats with diabetic cardiomyopathy.

Effects of MCC-135 on contraction and relaxation properties and sarcoplasmic reticulum (SR) function were investigated in the failing ventricular muscle due to diabetic cardiomyopathy. Wistar rats were made diabetic by a single injection of streptozotocin (40 mg/kg i.v.). Seven months later, the left ventricular papillary muscle was isolated and isometric tension was measured. The skinned fiber with functional SR preserved was prepared by treatment of the papillary muscle with saponin and used to study SR Ca(2+) uptake, Ca(2+) release, and Ca(2+) leakage. In diabetic rats, developed tension (DT) was decreased, and 80% relaxation time (TR80) and time to peak tension (TTP) were increased compared with normal rats. MCC-135 decreased TR80 and TTP without significant effect on DT in diabetic rats, but not in normal rats. Isoproterenol increased DT, and decreased TTP and TR80 only in normal rats. In diabetic rats, SR Ca(2+) uptake and SR Ca(2+) release were decreased, and SR Ca(2+) leakage was increased compared with normal rats. MCC-135 increased SR Ca(2+) uptake and decreased SR Ca(2+) leakage in diabetic rats, but not in normal rats. SR Ca(2+) release was not affected by MCC-135 both in normal and diabetic rats. The combination of protein kinase A and cAMP increased SR Ca(2+) uptake only in normal rats. These results suggest that MCC-135 has a positive lusitropic effect that might be associated with enhanced Ca(2+) uptake into the SR and reduced Ca(2+) leakage from the SR. MCC-135 appears to be more beneficial in treating the failing myocardium with lusitropic abnormality than cAMP-increasing drugs.
INTERNATIONAL OUTPUT AND INFLATION UNCERTAINTY AND THEIR IMPACT ON COUNTRIES' MACROECONOMIC PERFORMANCE. EVIDENCE FROM A DYNAMIC FACTOR GARCH-IN-MEAN MODEL

We identify international output and inflation uncertainty and analyze their impact on individual countries' macroeconomic performance. Output and inflation uncertainty on an international level is measured through the conditional variances of common factors in inflation and output growth, estimated from a bivariate dynamic factor model with GARCH errors. The impact of international and country-specific uncertainty is analyzed by including the conditional variances as regressors. We find increases in uncertainty during the first and second oil crisis, the 1980s and 1990s recessions as well as the recent Great Recession to be confined to the international level. The effect of international uncertainty results to be highly significant and unambiguously negative on countries' output growth and inflation rates whereas the impact of country-specific uncertainty is very mixed.
Gender, Mentoring and Social Capital in the National Health Service (NHS) in Scotland, UK

Abstract This chapter investigates the role of gender, mentoring and social capital and contributes to literature about the career development of women in senior management roles in the National Health Service of the UK. It draws on a doctoral study of senior-level managers in a Scottish NHS Board. The data collected are: (i) documentary; (ii) quantitative; and (iii) qualitative. The quantitative data are collected through questionnaires, while the source of qualitative data is in-depth semi-structured interviews. The doctoral study is embedded within an interpretivist and feminist paradigm. Although access to mentoring and social capital was seen as likely to enhance the career progression of females to senior managerial roles, gendered work and family expectations, gendered organisational culture, and normative performances of gendered senior management were identified as obstacles in taking advantages of mentoring and social capital. To the best of our knowledge, this is the only piece of work that explicitly investigates the role of mentoring and social capital in managing gender diversity at the senior managerial positions of the NHS.
Design and prototyping of dual layer linear arrays

This paper studies the designs and prototyping of dual layer linear arrays in a multiplexing configuration where each array element has one piezocomposite layer on top of the other. The arrays have 32 elements with 300 μm pitch and 60 μm kerf width. A composite of PZT and Spurr's epoxy in 2-2 connectivity is used as active layers. Two acoustic matching strategies were tested: A low frequency (LF) version to match for the two active layers electrically coupled in parallel, working at the center frequency 2.5 MHz, and a high frequency (HF) version to match for only the back layer working, at center frequency 5 MHz. Electrical impedances show fair agreement with the simulations, according to the center frequency and bandwidths. Pulse-echo measurement on the LF version showed that the width of the fundamental passband is in accordance with Mason model simulations, though the measured sensitivity is about 5 dB below the simulated values. The measured sensitivity of the third harmonic band is about 8 dB higher than that predicted by the Mason model. The differences can be attributed to imperfections in the fabrication process, especially to the bondline between the piezoelectric layers, which influenced the array performance.
Proteomic Analysis of the Quorum-Sensing Regulon in Pantoea stewartii and Identification of Direct Targets of EsaR

ABSTRACT The proteobacterium Pantoea stewartii subsp. stewartii causes Stewart's wilt disease in maize when it colonizes the xylem and secretes large amounts of stewartan, an exopolysaccharide. The success of disease pathogenesis lies in the timing of bacterial virulence factor expression through the different stages of infection. Regulation is achieved through a quorum-sensing (QS) system consisting of the acyl-homoserine lactone (AHL) synthase, EsaI, and the transcription regulator EsaR. At low cell densities, EsaR represses transcription of itself and of rcsA, an activator of the stewartan biosynthesis operon; it also activates esaS, which encodes a small RNA (sRNA). Repression or activation ceases at high cell densities when EsaI synthesizes sufficient levels of the AHL ligand N-3-oxo-hexanoyl-l-homoserine lactone to bind and inactivate EsaR. This study aims to identify other genes activated or repressed by EsaR during the QS response. Proteomic analysis identified a QS regulon of more than 30 proteins. Electrophoretic mobility shift assays of promoters of genes encoding differentially expressed proteins distinguished direct targets of EsaR from indirect targets. Additional quantitative reverse transcription-PCR (qRT-PCR) and DNA footprinting analysis established that EsaR directly regulates the promoters of dkgA, glpF, and lrhA. The proteins encoded by dkgA, glpF, and lrhA are a 2,5-diketogluconate reductase, glycerol facilitator, and transcriptional regulator of chemotaxis and motility, respectively, indicating a more global QS response in P. stewartii than previously recognized.
Use of photodynamic therapy and chitosan for inactivacion of Candida albicans in a murine model.

BACKGROUND The wide use of topical and systemic antifungal agents as the conventional treatment for oral candidiasis has caused Candida albicans to develop resistance to these agents. The aims of this study were to evaluate the effects of photodynamic therapy (PDT) and chitosan on buccal candidiasis and study the possible enhancive effect of chitosan on the photosensitizer methylene blue. METHODS Thirty-five DBA/2 immunosuppressed mice were orally inoculated with a suspension of Candida albicans. The animals were randomized into seven groups (n = 5 per group): Group 1 (control); Group 2 (nystatin); Group 3 (PDT); Group 4 (chitosan 1.5 mg/ml); Group 5 (chitosan 3 mg/ml); Group 6 (PDT + chitosan 1.5 mg/ml); and Group 7 (PDT + chitosan 3 mg/ml). The Candida albicans count was evaluated on days 3, 5, 7, and 11 after inoculation. At last, macroscopic and microscopic analyses of the tongue dorsa were performed. RESULTS On day 7 after inoculation, the control group showed a greater number of Candida albicans (5.25 ± 0.41 log10 CFU/ml), with significant differences compared to all other groups (P ≤ 0.05). On day 11 after inoculation, animals treated with PDT showed lower CFU/ml count. Groups 2, 3, 4, 5, and 6 showed fewer microscopic candidiasis lesions than Groups 1 and 7. CONCLUSIONS PDT has an antifungal effect, even greater than nystatin. Chitosan has a powerful fungicide effect but did not possess any enhancive effect on methylene blue.
Interval training in patients with severe chronic heart failure: analysis and recommendations for exercise procedures.

This study analyzes a new exercise training procedure, which includes interval exercise training on cycle ergometer (IntCT) (30-s work phases/60-s recovery phases) and on treadmill (60-s work and recovery phases each). Training was applied for 3 wk in 18 patients with severe chronic heart failure (CHF) ((mean +/- SEM) age 52 +/- 2 yr, ejection fraction 21 +/- 1%). Peak VO2 was increased from 12.2 +/- 0.7 to 14.6 +/- 0.7 ml-kg-1 min-1 owing to training (P < 0.001). A specific steep ramp test (work rate increments 25 W.10 s-1) was developed to derive exercise intensity for work phases in IntCT, which was 50% of the maximum work rate achieved. Steep ramp test was performed at the start of the study to determine the initial training work rate, then weekly to readjust it. Since the maximum work rate achieved from this test increased weekly (144 +/- 10 W -->172 +/- 10 W-->200 +/- 11 W; P < 0.001), the training work rate also increased (72 +/- 4 W-->86 +/- 6 W-->100 +/- 7 W; P < 0.001). Physical responses to IntCT were measured. There was no significant change in heart rate, blood pressure, and ratings of perceived exertion (RPE) using a Borg Scale between the first and the third week of training (heart rate 88 +/- 3 b.min-1; blood pressure 115 +/- 4/80 +/- 2 mm Hg; leg fatigue 12 +/- 1; dyspnea 10 +/- 1). Mean lactate concentration (1.70 +/- 0.09 mmol-1-1) indicated an overall aerobic range of training intensity. When compared with the commonly used intensity level of 75% peak VO2 from an ordinary ramp test (work rate increments 12.5 W.min-1), the performed training work rate was more than doubled (240%; P < 0.0001) while cardiac stress was lower (86%; P < 0.01). Values of norepinephrine and epinephrine as well as of RPE corresponded to those measured at 75% peak VO2. Interval exercise training is thus recommended for selected patients with CHF as it allows intense exercise stimuli on peripheral muscles with minimal cardiac strain. Using a steep ramp test, training work rate can be determined and readjusted weekly during initial training period.
An adaptive mechanism for LTE P-GW virtualization using SDN and NFV

Software Defined Networking (SDN) and Network Function Virtualization (NFV) paradigms have been widely used to redesign the traditional mobile networks. Despite several proposals on the literature, researchers have drawn limited attention to the virtualization of user-plane functions that demand high traffic volume processing, as the case of Long Term Evolution (LTE) mobile gateways. This paper introduces an adaptive mechanism for the user plane virtualization of the LTE Packet Data Network (PDN) GateWay (P-GW), running entirely on top of OpenFlow switches. Using both SDN and NFV concepts, the proposed mechanism employs elastic computing notions to dynamically activate or deactivate the infrastructure switches so the virtualized gateway can adjust to workload changes. This work addresses both software and hardware OpenFlow infrastructure platforms, and simulation results highlight the benefits that can be achieved by the presented mechanism.
Reforming US public sector plans : Truths and consequences

Most public-sector pension plans in the United States provide quite generous defined benefits. Long-term projections show that full payment of these promises threatens the finances of many state and local employers, which implies that taxes will have to be increased or pensions and/or other public expenditures reduced. This article analyzes the effectiveness of measures aimed at improving the sustainability of these plans.We consider the impact of contribution increases, benefit reductions, and adjustments in the pension fund’s investment strategy. Since a pension fund can be seen as a zero-sum game, these interventions imply value redistributions among current and future plan participants and current and future tax payers. We use the value-based asset–liability management (ALM) method to estimate the value of those transfers. These imply massive value redistributions from taxpayers to plan participants that could exceed 20% of American GDP. Hence, plan sustainability may be achieved only through either substantially higher contributions or lower benefits.
The Relationship Between Perceived Social Capital and the Health Promotion Willingness of Companies: A Systematic Telephone Survey With Chief Executive Officers in the Information and Communication Technology Sector

Objective: This study examines the association between perceived social capital and health promotion willingness (HPW) of companies from a chief executive officer's perspective. Methods: Data for the cross-sectional study were collected through telephone interviews with one chief executive officer from randomly selected companies within the German information and communication technology sector. A hierarchical multivariate logistic regression analysis was performed. Results: Results of the logistic regression analysis of data from a total of n = 522 interviews suggest that higher values of perceived social capital are associated with pronounced HPW in companies (odds ratio = 3.78; 95% confidence intervals, 2.24 to 6.37). Conclusions: Our findings suggest that characteristics of high social capital, such as an established environment of trust as well as a feeling of common values and convictions could help promote HPW.
The lived experience of parents enabling participation of their child with a physical disability at home, at school and in the community

Abstract Purpose: The aim of this study was to provide an in-depth exploration and understanding of parents’ thoughts, feelings and concerns they experience while reflecting on their actions, challenges and needs in enabling their child’s participation at home, at school and in the community. Method: A naturalistic inquiry with thirteen Dutch parents using interpretative phenomenological analysis. Results: Analysis revealed three super-ordinate themes: “Parents’ experiences and concerns about systems, laws and regulations”, “Parents’ experiences and thoughts about physical and/or social environment” and “Parents’ experiences and feelings of finding and/or enabling an activity”. Parents’ often expressed feelings of disappointment derived from being misunderstood, from dealing with the complexity of systems, from hindrance of participation of their children by the social and the physical environment, and from the lack of leisure activities for their child. It is primarily restrictions in the physical and social environments that urge them to take actions, to experience challenges and think of needs. Conclusions: In-depth exploration and understanding of parents’ articulated matters must be shared and taken seriously by policymakers and service providers. Parents’ knowledge and experiences should be of major relevance to improve paediatric rehabilitation and other services for children with a physical disability. Implications for Rehabilitation To achieve tailored pediatric rehabilitation, involvement and needs of parents in enhancing their child’s participation ought to be acknowledged. Active use of parents’ experiences and knowledge regarding the participation of their child on different levels of decision making may improve daily services in pediatric rehabilitation. Aiming for optimal participation of a child with a physical disability at home, at school and in the community, the focus of pediatric rehabilitation needs to shift towards enabling, social and physical, environments.