Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantification of Transthyretin Kinetic Stability in Human Plasma Using Subunit Exchange

The transthyretin (TTR) amyloidoses are a group of degenerative diseases caused by TTR aggregation, requiring rate-limiting tetramer dissociation. Kinetic stabilization of TTR, by preferential binding of a drug to the native tetramer over the dissociative transition state, dramatically slows the progression of familial amyloid polyneuropathy. An established method for quantifying the kinetic stability of recombinant TTR tetramers in buffer is subunit exchange, in which tagged TTR homotetramers are added to untagged homotetramers at equal concentrations to measure the rate at which the subunits exchange. Herein, we report a subunit exchange method for quantifying the kinetic stability of endogenous TTR in human plasma. The subunit exchange reaction is initiated by the addition of a substoichiometric quantity of FLAG-tagged TTR homotetramers to endogenous TTR in plasma. Aliquots of the subunit exchange reaction, taken as a function of time, are then added to an excess of a fluorogenic small molecule, which immediately arrests further subunit exchange. After binding, the small molecule reacts with the TTR tetramers, rendering them fluorescent and detectable in human plasma after subsequent ion exchange chromatography. The ability to report on the extent of TTR kinetic stabilization resulting from treatment with oral tafamidis is important, especially for selection of the appropriate dose for patients carrying rare mutations. This method could also serve as a surrogate biomarker for the prediction of the clinical outcome. Subunit exchange was used to quantify the stabilization of WT TTR from senile systemic amyloidosis patients currently being treated with tafamidis (20 mg orally, once daily). TTR kinetic stability correlated with the tafamidis plasma concentration.
Continuous Measurement of Endotracheal Tube Cuff Pressure: How Difficult Can It Be?

Continuous monitoring and download of endotracheal tube cuff pressure for a 12-hour period were required to collect data for an ongoing program of research related to airway management of the critically ill patient. On the basis of reports from the anesthesia literature, continuous monitoring of cuff pressure via a traditional pressure transducer and monitor was identified as the best method to collect data. Although continuous pressure monitoring of many physiologic variables is routine in critical care settings, application of the technology to measurement of endotracheal tube cuff pressure has not been reported outside the operating room. The research team conducted bench testing and pilot testing in human subjects to establish feasibility, accuracy, and safety of continuous cuff pressure monitoring. Monitoring was feasible with stringent procedures applied to ensure safety. A bias of 0.5 cm H2O between continuous and intermittent measures was obtained in both in vitro and in vivo testing.
MRI artifact reduction and quality improvement in the upper abdomen with PROPELLER and prospective acquisition correction (PACE) technique.

OBJECTIVE The purpose of this study was to evaluate the effectiveness of the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER [BLADE in the MR systems from Siemens Medical Solutions]) with a respiratory compensation technique for motion correction, image noise reduction, improved sharpness of liver edge, and image quality of the upper abdomen. SUBJECTS AND METHODS Twenty healthy adult volunteers with a mean age of 28 years (age range, 23-42 years) underwent upper abdominal MRI with a 1.5-T scanner. For each subject, fat-saturated T2-weighted turbo spin-echo (TSE) sequences with respiratory compensation (prospective acquisition correction [PACE]) were performed with and without the BLADE technique. Ghosting artifact, artifacts except ghosting artifact such as respiratory motion and bowel movement, sharpness of liver edge, image noise, and overall image quality were evaluated visually by three radiologists using a 5-point scale for qualitative analysis. The Wilcoxon's signed rank test was used to determine whether a significant difference existed between images with and without BLADE. A p value less than 0.05 was considered to be statistically significant. RESULTS In the BLADE images, image artifacts, sharpness of liver edge, image noise, and overall image quality were significantly improved (p < 0.001). CONCLUSION With the BLADE technique, T2-weighted TSE images of the upper abdomen could provide reduced image artifacts including ghosting artifact and image noise and provide better image quality.
The notion of well-being in the New Zealand education system

This article engages with the notion of well-being in two ways: it explores how well-being is constructed and used in the two New Zealand national curriculum documents, Te Whāriki: He Whāriki Mātauranga Mō nga Mokopuna o Aotearoa/Early Childhood Curriculum (Ministry of Education [MoE], 1996) and the New Zealand Curriculum for English-medium Teaching and Learning in Years 1-13 (MoE, 2007); and how well-being is considered more broadly in the field of education and in relation to historical, philosophical traditions. This article aims not to make claims and statements about the role of well-being in (early childhood) education, but to encourage the reader to consider the importance of students’ well-being for educational theory and practice and to reflect on one’s own practice and role as educator to this end.
Tail Risk Mitigation with Managed Volatility Strategies

Managed volatility strategies adjust market exposure in inverse relation to a risk estimate, to stabilize realized portfolio volatility through time. Our paper examines strategy performance from an investment practitioner perspective. Using long-term data from the Standard & Poor’s 500, we show that these strategies offer an improvement in risk-adjusted return compared with a buy-and-hold benchmark, on average, but with some variation. Managed volatility strategies achieve robust tail-risk reduction while also enhancing skewness. These return normalization features are inherently linked to the nature of the volatility stabilization mechanism. We illustrate them via utility-based metrics that reward the tail-risk reduction emanating from volatility stabilization. These enhancements are economically meaningful for many time horizons and holding period combinations, and they remain once transaction costs have been included, suggesting a durable and tangible value-add from managed volatility strategies. They also suggest a more appropriate way to measure the performance improvements of tail-risk-mitigating strategies.
Synthetic Peptides Containing ITIM-Like Domains Block Expression of Inflammatory Mediators and Migration/Invasion of Cancer Cells Through Activation of SHP-1 and PI3K

Increasing evidence supports that inflammation is closely associated with the development of cancer. In an effort to develop synthetic peptides that can suppress the inflammatory activation of cancer cells, decapeptides representing immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences of immune receptor expressed on myeloid cells-1 (IREM-1) were tested for their anti-inflammatory effects in cancer cell lines. One (named TAT-YADL) out of the five synthetic peptides tested exhibited inhibitory effects on the expression of inflammatory mediators as well as invasion and migration. The inhibitory activities of the synthetic peptides required activation of SH2-containing protein tyrosine phosphatase-1 (SHP-1) and phosphoinositide 3-kinase (PI3K).
Why Do Migrant Workers Rely More Often on Referrals?

Intuitively, one can expect that migrant workers have smaller social networks in the new destination country and by that smaller probability of finding a job through referrals. However, empirical analysis of the SOEP data from 2002 to 2008 show that 41.21% of migrant workers and 31.79% of native workers found their current job through referrals. Estimation results of the panel probit model with random effects show that 7.26% statistically significant difference of the predicted probabilities of using referrals between migrant and native workers is not explained by the characteristics of the individuals and firms. In order to explain this puzzle, this paper presents a search and matching model with heterogeneous worker groups and several search channels. The firm observes the noisy signal of the productivity, the nationality and the search channel of the worker to form unbiased expectations about the true productivity of the worker. The probabilities to be hired for the two worker groups and different search channels are determined using ex-ante union bargained wage and expectations of the firm. Calibration results of the model show that even when migrant workers have smaller size of the social network, they gain more from recommendations, because their employment chances are initially much lower than employment chances of native workers.
Analysis of micronuclei in blue mussels and fish from the Baltic and North Seas

Micronuclei (MN) were analyzed in erythrocytes of flounder (Platichthys flesus) and wrasse (Symphodus melops) and in gill cells of blue mussels (Mytilus edulis). The organisms were collected from three study stations in the Baltic Sea and from seven stations in the North Sea (Karmsund area, Norway) 4 times. The statistically significant differences obtained were related to the season, sex of the fish, and sampling locality. Higher MN frequencies were found in fish and mussels collected from the most polluted study stations in the North Sea. The same tendency could be described in the Baltic Sea; however, it was masked by the recent oil spill from the Butinge oil terminal. Our results showing higher MN frequencies in presumably what were the most polluted study locations suggest that MN tests in fish and mussels may be used for the detection of genotoxic effects in a marine environment. The endpoint is well characterized and can be easily recognized, and the technique is convenient to use in field samplings following standard procedures and protocols. © 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 365–371, 2004.
ThinPrep® vs. conventional smear cytologic preparations in analyzing fine‐needle aspiration specimens from palpable breast masses

Limited data exist concerning the cellular features of the ThinPrep® (Cytyc Corp., Boxborough, MA) technique in the analysis of breast fine‐needle aspiration specimens. Therefore, we analyzed a series of 75 surgically excised palpable breast masses and compared ThinPrep and conventional smear fine‐needle aspiration preparations. Each mass was aspirated twice. The first sample was used for two alcohol‐fixed conventional smears, and the second sample was rinsed into CytoLyt (Cytyc Corp., Boxborough, MA) solution for processing into a ThinPrep slide. The paired slides were separated and independently analyzed for adequacy, overall cellularity, single epithelial cells (absent, rare, moderate, or numerous), epithelial architecture (sheets or three‐dimensional clusters), myoepithelial cells and stripped bipolar nuclei (present or absent), and nuclear detail (poor, satisfactory, or excellent). Each sample was classified as negative, negative consistent with fibroadenoma, atypical favoring benign, atypical favoring malignant, or positive for malignant cells. The 75 breast masses included 32 carcinomas and 43 benign lesions. Four conventional smears and one ThinPrep were unsatisfactory. Significantly, more conventional smears were limited by drying artifact (9 vs. 0). ThinPrep aspirates of carcinomas had better nuclear detail (P = 0.03) and greater cellularity (P = 0.05). ThinPrep aspirates of benign masses had greater epithelial cellularity (P = 0.007) and better nuclear detail (P < 0.001), and more specimens had myoepithelial cells (P = 0.007). The ThinPrep interpretation classified 29 of 32 carcinomas (91%) as positive and three as atypical favoring malignant (sensitivity = 100%). The conventional smear interpretation classified 28 of 31 carcinomas (90%) as positive and three as atypical favoring malignant (sensitivity = 100%). The ThinPrep interpretation classified 42 benign lesions as negative (23 cases), negative consistent with fibroadenoma (8 cases), atypical favoring benign (10 cases), and atypical favoring malignant (1 case) (specificity = 74%). The conventional smear interpretation classified 40 benign lesions as negative (25 cases), negative consistent with fibroadenoma (12 cases), and atypical favoring benign (3 cases) (specificity = 93%). ThinPrep was less specific, but the difference was not statistically significant (P = 0.065). In summary, ThinPrep aspirates had greater cellularity and better nuclear detail than conventional smears, and were just as sensitive in identifying the carcinomas. The difference in specificity between the two techniques was not statistically significant (P = 0.065). Diagn. Cytopathol. 1999;21:137–141. © 1999 Wiley‐Liss, Inc.
Contribution of thermolabile methylenetetrahydrofolate reductase variant to total plasma homocysteine levels in healthy men and women. Inter99 (2)

Elevation in plasma total homocysteine (tHcy) is believed to be causally related to cardiovascular disease. Like age and sex, the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR(C677T)) is an important nonmodifiable determinant of tHcy, which may be considered when describing normal ranges of tHcy in the general population. We investigated the simultaneous effect of sex, age, and MTHFR(C677T) genotype on the distribution of tHcy in a cross‐sectional study design. THcy concentrations and MTHFR(C677T) genotype were determined in a population‐based sample of 2,788 Danish men and women aged 30–60 years participating in the Inter99 Study. The prevalences of MTHFR(C677T) genotypes were 48.8% (CC), 42.4% (CT), and 8.8% (TT). The overall median tHcy was 8.1 µmol/l, and the 2.5–97.5 percentiles were 4.8–17.8 µmol/l. The estimated proportionally higher level of tHcy in men compared to women was 14.3% (P<0.001). A significant interaction term was found between age and MTHFR(C677T) genotype (P<0.001). The estimated changes in tHcy per 5 years of age were 1.5% in CC individuals (P<0.01), 2.1% in CT individuals (P<0.001), and −4.1% in TT individuals (P<0.01). The T allele was associated with elevated tHcy. However, the proportionally higher level of tHcy in TT individuals compared to CT and CC individuals decreased with increasing age. The MTHFR(C677T) polymorphism explained 6% of the phenotypic variation in tHcy. In conclusion, we found that tHcy is associated with sex, age, and MTHFR genotype. Our results indicate that the effect of age is modified by MTHFR genotype. Genet Epidemiol 24:322–330, 2003. © 2003 Wiley‐Liss, Inc.
Web-Based Tailored Lifestyle Programs: Exploration of the Target Group's Interests and Implications for Practice

An important challenge in Web-based health promotion is to increase the reach of the target audience by taking the target groups' desires into consideration. Data from 505 members of a Dutch Internet panel (representative for Dutch Internet users) were used to asses the target group's interests and needs. 28% participated in Web-based tailored lifestyle programs, 57% expressed an interest in such programs, and 15% expressed no interest. Interest in Web-based programs was predominantly caused by a general interest in lifestyle and online tests. Participation in Web-based tailored lifestyle programs should not take more than 17 minutes per occasion. 84% were interested in follow-up testing after the initial participation. Responders were particularly interested in physical activity and nutrition. Hardly anyone was willing to pay for participation. The results from this study support the use of Web-based tailored lifestyle programs in behavior change efforts.
The Burra Charter of Australia ICOMOS in 1983

This paper is reprinted at the suggestion of the author' from Protecting the Past for the Future: Proceedings of the Unesco Regional Conference an Historic Places Sydney 22-28 May 1983 edited by Max Bourke, Miles Lewis and Bal Saini (Canberra: Australian Government Publishing Service 1983).
Tcf7l1 protects the anterior neural fold from adopting the neural crest fate

The neural crest (NC) is crucial for the evolutionary diversification of vertebrates. NC cells are induced at the neural plate border by the coordinated action of several signaling pathways, including Wnt/β-catenin. NC cells are normally generated in the posterior neural plate border, whereas the anterior neural fold is devoid of NC cells. Using the mouse model, we show here that active repression of Wnt/β-catenin signaling is required for maintenance of neuroepithelial identity in the anterior neural fold and for inhibition of NC induction. Conditional inactivation of Tcf7l1, a transcriptional repressor of Wnt target genes, leads to aberrant activation of Wnt/β-catenin signaling in the anterior neuroectoderm and its conversion into NC. This reduces the developing prosencephalon without affecting the anterior-posterior neural character. Thus, Tcf7l1 defines the border between the NC and the prospective forebrain via restriction of the Wnt/β-catenin signaling gradient. Summary: In developing mouse embryos, Tcf7l1 defines the border between the neural crest and the prospective forebrain via restriction of the Wnt/β-catenin signaling gradient.
Follow the leader? Conceptualising the relationship between leaders and followers in polycentric climate governance

ABSTRACT Existing scholarship on climate governance has not sufficiently considered the relationship between climate leaders/pioneers and followers. Because of the global commons nature of climate change, unilateral leadership or pioneership by one or a small number of actors will be insufficient to combat climate change effectively. The need to take seriously the relationship between leaders and followers is all the greater in the wake of the 2015 Paris Agreement, which emphasises diffuse, bottom–up action. The relationship between leaders and followers in polycentric climate governance is unpacked in this contribution. What types of actors can be climate followers? Through what pathways can followership emerge and how can we capture the essential characteristics of leader–follower relationships? What conditions facilitate (or hinder) followership? The utility of the approach is illustrated using cases of EU climate leadership and (non-) followership of other actors.
Importance Sampling Applied to Greeks for Jump–Diffusion Models with Stochastic Volatility

We develop a variance reduction technique, based on importance sampling in conjunction with the stochastic Robbins–Monro algorithm, for option prices of jump–diffusion models with stochastic volatility. This is done by combining the work developed by Arouna for pricing diffusion models, and extended by Kawai for Lévy processes without a Brownian component. We apply this technique to improve the numerical computation of derivative price sensitivities for general Lévy processes, allowing both Brownian and jump parts. Numerical examples are performed for both the Black–Scholes and Heston models with jumps and for the Barndorff–Nielsen–Shephard model to illustrate the efficiency of this numerical technique. The numerical results support that the proposed methodology improves the efficiency of the usual Monte Carlo procedures.
A Universe of Stories: Mobilizing Narrative Practices During Transformative Change

Constructing narratives of transformative change is an important but challenging practice through which strategy makers attempt to influence acceptance of an ongoing transformation. To understand whether and how strategy makers can construct a steady influx of captivating narratives of transformative change, we analyzed how one noted strategy maker assisted the successful transformation of his organization over three decades by orchestrating the production of change narratives. Our analysis reveals that the strategy maker constructed and reconstructed meanings of change over time using three sets of distinct but interconnected narrative practices. We develop a dynamic model linking the simultaneous mobilization of these practices to strategy makers’ ability to harness the persistent tension between novelty and familiarity in a transformative change, and thereby win endorsement from key audiences.
A new iterative phase correction algorithm in conformal antenna array designing

Compared with ordinary linear antenna arrays or planar antenna arrays, space conformal antenna array has many advantages, such as the flexibility and accuracy of the beam. However, conventional algorithms cannot be applied to the designing of conformal antenna arrays, so the weighted minimum mean square error algorithm is proposed. In this paper, a new iterative phase correction algorithm is presented to improve the weighted minimum mean square error (MMSE) algorithm. By using the new algorithm, the shape of the beam can be controlled more flexibly, and more interferences can be resisted compared with the weighted minimum mean square error algorithm. The simulation results show an improved performance in beamforming.
Redefining the Role of psr in β-Lactam Resistance and Cell Autolysis of Enterococcus hirae

ABSTRACT The contribution of penicillin-binding protein 5 (PBP5) and the PBP5 synthesis repressor (Psr) to the β-lactam resistance, growth, and cell autolysis of wild-type strain ATCC 9790 and resistant strain R40 of Enterococcus hirae was investigated by disruption or substitution of the corresponding pbp5 and psr genes by Campbell-type recombination. The resulting modifications were confirmed by hybridization and PCR. The low susceptibility of E. hirae to β-lactams was confirmed to be largely dependent on the presence of PBP5. However, against all expectations, inactivation of psr in ATCC 9790 or complementation of R40 cells with psr did not modify the susceptibility to benzylpenicillin or the growth and cell autolysis rates. These results indicated that the psr gene does not seem to be involved in the regulation of PBP5 synthesis and consequently in β-lactam resistance or in the regulation of cell autolysis in E. hirae.
Automated Blood Pressure Recording: The Phenomenon of Blood Pressure Elevations During Speech

The recent development of automatic non-invasive blood pressure devices has allowed the rapid and repeated assessment of both the blood pressure and pulse rate in the clinical setting. The development of this technology has allowed us to observe a striking relationship between human communication and blood pressure. Talking produces rapid increases in their systolic, diastolic and mean arterial pressures as well as pulse rate in both normotensive and hypertensive subjects. This phenomenon has been obscured by the conven tional assessment techniques of blood pressure measurement. Ignoring the pattern of verbal communication during the assessment of blood pressure can result in marked differences in recorded blood pressure and its interpretation.