Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick Type B disease

Niemann Pick disease (NPD) is an autosomal recessive lysosomal storage disorder caused by the deficient activity of acid sphingomyelinase due to mutations in the SMPD1 gene. We functionally characterized three novel SMPD1 mutations and 11 already reported in the Italian population. Mutant alleles were studied for enzyme activity and protein processing in transiently transfected COS‐1 cells. The c.96G>A, c.100delG, c.565dupC, and c.575dupC (p.W32X, p.G34fsX42, p.P189fsX1, and p.P192fs14) alleles expressed no immunoreactive protein and consequently no enzyme activity. In contrast, cells transfected with mutants c.308T>C, c.389T>C, c.674T>C, c.732G>C, c.841G>A, c.1687G>A, c.1799G>A, and c.1799G>C (p.L103P, p.V130A, p.L225P, p.W244C, p.A281T, p.D563Y, p.R600H, p.R600P) expressed protein levels comparable to wild‐type ASM expressing cells. Only three of these constructs, c.389T>C, c.1687G>A, and c.1799G>A (p.V130A, p.D563Y, p.R600H), retained residual activity while the other five expressed very low or no enzyme activity. As expected, the c.1669underscore;1670delGT (p.V557fsX18) mutant expressed a completely inactive truncated protein. Interestingly, the c.2T>G (p.M1_W32del) mutant expressed 26.9% of the wild type activity, even though no ASM protein was detected by Western blot analysis, suggesting that the amount of produced enzyme is below detection levels. The results presented in this study are consistent with the wide phenotype variability found in NP type B patients and provide valuable insights into the molecular basis of the disease. © 2005 Wiley‐Liss, Inc.
Integrin expression in colon cancer cells is regulated by the cytoplasmic domain of the β6 integrin subunit

We have previously reported that the αvβ6 integrin upregulates its own expression in a protein kinase C‐dependent manner with increasing cell density. The wild‐type β6 integrin subunit has also been shown to promote tumour growth in vivo and its growth‐enhancing effect is regulated by both a MAP kinase binding motif on β6 and the 11 amino acid C‐terminal cytoplasmic extension unique to the β6 subunit. Herein, we show that the 11 amino acid cytoplasmic extension is essential for the cell density‐dependent increase in β6 expression and that the 11 amino acid tail exerts a dominant negative effect on cell density‐ and PKC‐mediated β5 expression in αvβ6‐expressing colon cancer cells. Cells that express β6 lacking the 11 amino acid tail respond to PKC simulation with increased expression of only the β5 subunit as seen for cells that lack constitutive αvβ6 expression. In contrast, loss of the ERK binding site on β6 markedly impairs cell density‐ and PKC‐dependent expression of either β6 or β5 in the presence or absence of the 11 amino acid tail, respectively. Our findings suggest that in αvβ6‐expressing cells, a hierarchy of kinase signalling cascades exists and that the β6‐ERK2 interaction dominates over PKC‐mediated signalling pathways responsible for integrin upregulation with cell confluence. Given the dominance of the β6‐ERK2 interaction over PKC‐mediated expression of both β5 and β6 integrin subunits, targeting the β6‐ERK2 interaction may prove useful as an anticancer strategy in colon cancer. © 2002 Wiley‐Liss, Inc.
Research work as curriculum work in New Zealand early childhood settings: What should be taught and learned?

Abstract This article draws from experiences in an ongoing study of children’s narrative competence in the early years across early childhood education and school settings. Focusing on the research as it is being conducted in the early childhood context (a kindergarten), the paper inquires into what it means to do research in education settings where curriculum is constituted as everything that happens there, and principles of curriculum demand empowering, responsive and reciprocal, inclusive and holistic practices. Questions of research ethics, children’s rights to assent or dissent to participate, to learn about the findings and consequences of the research, and to have the research recognised as curriculum experience are raised. Sitting at the intersection of research work and pedagogical/curriculum work the paper explores lessons from New Zealand of striving towards a fuller curriculum policy implementation and of addressing demands for ethical research practices with children who are very young.
The Betting Against Beta Anomaly: Fact or Fiction?

This paper suggests an alternative explanation for the recently documented betting against beta anomaly. Given that the equity of a levered firm is equivalent to a call option on firm assets and option returns are non-linearly related to underlying stock returns, linear CAPM-type regressions are generally misspecified. We derive theoretical expressions for the pricing error and analyze its magnitude using numerical examples. Consistent with the empirical findings of Frazzini and Pedersen (2014), our pricing errors are negative, increase with leverage, and become economically significant for higher levels of firm leverage.
Purification and N-terminal amino acid sequences of Chlamydia trachomatis histone analogs

DNA-binding proteins specific to Chlamydia trachomatis elementary bodies have been described and recently characterized as procaryotic histone analogs. I have developed an affinity purification procedure for the 18-kDa histone analog, Hc1, based on its affinity for polyanions. The availability of highly purified Hc1 has allowed for determination of its N-terminal amino acid sequence and should prove useful in studies of its biological function. The variable C. trachomatis histone analog not obtained by this procedure was electrophoresed onto Immobilon paper for sequencing. The N terminus of the variable histone was conserved among C. trachomatis serotypes L2, D, and B and was distinct from that of Hc1.
Gliding Motion Regulation of a Robotic Dolphin Based on a Controllable Fluke

This paper investigates a controllable fluke's regulation effect on the gliding motion of a self-propelled robotic dolphin in both theory and practice. In theory, based on a dynamic model, the gliding equilibria is first analyzed. Through deriving the explicit expressions of the pitch angle, gliding angle, and velocities, we explore how the deflection angle of the controllable fluke changes the gliding performance. Then, aided by these theoretical analyses, a pitch control strategy relying on the fluke is constructed. In simulations, the robotic dolphin is able to track a given pitch angle during gliding, directly through adopting this control strategy to regulate the fluke's deflection angle. Furthermore, extensive gliding experiments in different fluke's deflection angles are carried out. From the statistical data, we further explore the remarkable effects of the controllable fluke on the gliding performance in practice. Besides, the other pitch control experiment is also executed to validate the effectiveness of the proposed control approach. The results of this paper shed light on improving the gliding performance of the robotic dolphin in future mechanical design and gliding control.
Frontier Production Functions and Technical Progress: A Study of General Milk Processing in Swedish Dairy Plants

Technical change in general milk processing is estimated within a homothetic frontier production function allowing neutrally variable scale elasticity. The results show that technical progress is characterized by a rapid increase in optimal scale and a small capital saving bias, increasing the marginal productivity of labour relative to capital. To characterize technical change, Salter's measures of bias and technical advance are utilized and interpreted within the framework of the efficiency cancepts of Farrell.
Experiences with family group decision making in rural Ontario

This thesis explores the alternative dispute resolution method of family group decision making that is used in child welfare in Ontario. Using a qualitative case study, my research sought to answer the question: What are the experiences of caregivers who have participated in family group decision making in the District of Algoma? I examined the legislative framework, policy directive and guiding policies surrounding the use of FGDM in child welfare in the District of Algoma in rural Ontario. I also collected data through interviews with five participants and transcribed and analyzed using thematic analysis. The themes that emerged relate to the process of FGDM empowering families, the outcomes for children, and the ability for families to implement and maintain longterm plans for children. These themes and sub themes are discussed along with the implications for policy and practice and directions for future research.
Unraveling the Complexities of SIRT1-Mediated Mitochondrial Regulation in Skeletal Muscle

Sirtuin 1 (SIRT1) is a purported central regulator of skeletal muscle mitochondrial biogenesis. Herein, we discuss our recent work using conditional mouse models, which highlight the complexities of SIRT1 biology in vivo, and question the role of SIRT1 in regulating mitochondrial function and mitochondrial adaptations to endurance exercise. Furthermore, we discuss the possible contribution of proposed SIRT1 substrates to muscle mitochondrial biogenesis.
Carbon Emissions and Stock Returns

This paper provides an empirical investigation of the eect of the European Union's Emissions Trading Scheme (EU ETS) on German stock returns. In the initial two phases of the EU ETS, beginning in 2005 and ending in 2012, …rms received free allowances for emitting carbon dioxide. We …nd that …rms which received carbon emission allowances signi…cantly outperformed …rms which did not. This suggests the presence of a large and statistically signi…cant "carbon premium"de…ned as the abnormal excess return of the portfolio of "dirty"…rms minus that of the portfolio of "clean"…rms. The carbon premium is up to 18% per annum, it cannot be explained by movements in the price for carbon allowances, and is unrelated to industry eects, size and market-to-book ratios.
Towards expansive apprenticeships : a commentary by the Teaching and Learning Research Programme

The Teaching and Learning Research Programme (TLRP), managed by the Economic and Social Research Council (ESRC) in the UK, aims to shed light on learning and teaching throughout life, and to produce findings which will help improve educational outcomes for people of all ages. This commentary is a contribution to the public debate on apprenticeships and on the UK government's plans for the continued improvement of apprenticeship provision. It calls for apprenticeships as a model of learning to be placed at the heart of debates about vocational education and training for young people and adults. This requires a step change if policy decisions are to focus on the quality of the learning experience rather than viewing apprenticeships as yet another 'scheme' intended to meet government targets for increased numbers in post-compulsory education or training, or for the number of qualifications issued. In recent years, apprenticeships' core identity as a model of learning has been replaced by that of a policy instrument. In that sense, apprenticeships are currently government-owned and directed. This change has to be reversed.
MRI of atherosclerosis

The emergence of high‐resolution, rapid imaging methods has enabled MRI to noninvasively image the fine internal structure of atherosclerotic artery walls. This capability has, in turn, captured the interest of clinicians, who see it as an opportunity to assess disease severity based on the characteristics of atherosclerotic lesions themselves, rather than only their effects on the vessel lumen. MRI of atherosclerosis thus has the potential to be used in medical treatment decisions or to assess the effects of experimental treatment options. Given this potential, a number of research groups have been investigating MRI of atherosclerosis in an effort to establish the ability of MRI to determine atherosclerotic plaque burden, detect plaque composition, and ultimately identify vulnerable plaque before it leads to a clinical event. In this review, the current state of the art is summarized for the three primary vessel targets: the carotid artery, the aorta, and the coronary arteries. J. Magn. Reson. Imaging 2004;19:710–719. © 2004 Wiley‐Liss, Inc.
Early intervention for mild cognitive impairment: a randomised controlled trial

Background: Positive effects are reported for memory training for healthy older adults, and yet there is limited information about the benefit of cognitive intervention for older adults with increasing memory difficulties—mild cognitive impairment. Objective: To investigate the usefulness of an early cognitive intervention for the memory difficulties experienced by people with amnestic mild cognitive impairment. Methods: Using a randomised control design, 52 participants with amnestic mild cognitive impairment and their family partners were randomly assigned to a cognitive intervention (memory rehabilitation group) or waitlist (control group). Participants were assessed on primary measures of everyday memory (prospective memory) and memory strategies at 2 weeks’ and 4 months’ follow-up; secondary measures of contentment with memory and the family participants’ knowledge of memory strategies were also assessed. Results: Everyday memory, measured by performance on prospective memory tasks, significantly improved following intervention, although self-appraisal of everyday memory did not demonstrate a similar intervention effect. Knowledge and use of memory strategies also significantly increased following intervention. Furthermore, family knowledge of memory strategies increased following intervention. There was a strong trend towards improvement in contentment with memory immediately following intervention, but this effect was not significant. Conclusions: Early intervention for memory difficulties in amnestic mild cognitive impairment, using cognitive rehabilitation in compensatory strategies, can assist in minimising everyday memory failures as evaluated by performance on prospective memory tasks and knowledge of memory strategies.
The wound/burn guidelines – 3: Guidelines for the diagnosis and treatment for diabetic ulcer/gangrene

We aimed to prepare guidelines for the management of diabetic ulcer/gangrene with emphasis on the diagnosis and treatment of skin symptoms. They serve as a tool to improve the quality of the diagnosis and treatment in each patient and, further, to improve the level of the care for diabetic ulcer in Japan by systematically presenting evidence‐based recommendations for clinical judgments by incorporating various viewpoints.
Myeloid Tribbles 1 induces early atherosclerosis via enhanced foam cell expansion

Trib1 controls atherosclerotic plaque macrophage function by up-regulating OLR1, promoting foam cell formation and atherosclerosis. Macrophages drive atherosclerotic plaque progression and rupture; hence, attenuating their atherosclerosis-inducing properties holds promise for reducing coronary heart disease (CHD). Recent studies in mouse models have demonstrated that Tribbles 1 (Trib1) regulates macrophage phenotype and shows that Trib1 deficiency increases plasma cholesterol and triglyceride levels, suggesting that reduced TRIB1 expression mediates the strong genetic association between the TRIB1 locus and increased CHD risk in man. However, we report here that myeloid-specific Trib1 (mTrib1) deficiency reduces early atheroma formation and that mTrib1 transgene expression increases atherogenesis. Mechanistically, mTrib1 increased macrophage lipid accumulation and the expression of a critical receptor (OLR1), promoting oxidized low-density lipoprotein uptake and the formation of lipid-laden foam cells. As TRIB1 and OLR1 RNA levels were also strongly correlated in human macrophages, we suggest that a conserved, TRIB1-mediated mechanism drives foam cell formation in atherosclerotic plaque and that inhibiting mTRIB1 could be used therapeutically to reduce CHD.
Damage suffered by swamp morning glory (Ipomoea aquatica Forsk) exposed to vanadium (V)

To elucidate the physiological and morphological responses generated by vanadium (V) in plants, hydroponic culture experiments were performed with swamp morning glory (Ipomoea aquatica Forsk) exposed to 0 mg L−1 to 2.50 mg L−1 pentavalent V [V(V)] in Hoagland nutrient solutions. The concentration of chlorophyll a, chlorophyll b, and carotene peaked at a V(V) concentration of 0.05 mg L−1 and gradually decreased at higher V(V) concentrations. Similarly, the plant biomass was stimulated at low levels of V(V) and was inhibited when V(V) concentrations exceeded 0.1 mg L−1. Pentavalent V had negative effects on the uptake of phosphorus (P) by roots, shoots, and leaves. The biological absorption coefficients of V of the roots were higher than those of the aerial parts. Under low concentrations of V(V) exposure, the predominant species of V in the aerial parts was tetravalent V [V(IV)], whereas V(V) became more prevalent when concentrations of V(V) in the solution was higher than 0.50 mg L−1. In the roots, however, the concentrations of V(V) were always higher than those of the V(IV), except in the control group. Organelles in the V(V)‐treated leaves were distorted, and the periplasmic space became wider. These results indicate V(V) has concentration‐dependent effects on the physiological properties of swamp morning glory, whereas the plant has the ability to develop self‐protective function to adapt to the toxicity of V(V). Environ Toxicol Chem 2016;35:695–701. © 2015 SETAC
Electricity Demand in Wholesale Italian Market

Abstract In this paper we pursue two objectives: firstly we construct a theory based behavioral model of electricity demand in the Italian market; secondly we measure demand elasticity at hourly level, directly from consumer behavior. This is a novel approach providing the first attempt in the literature to estimate demand elasticity using individual demand bid data in the Italian Power Exchange (IPEX). Econometric estimation allows us to identify robust results, showing that elasticity varies significantly with: time of the day; day of the week; season of the year; pattern of line congestion; as well as according to the level of equilibrium price. This has meaningful policy implications: fostering more competition on the supply side could yield lower equilibrium prices and proportionately much higher quantities, for a lower offer curve shifted to the right would intersect a flatter portion of the demand curve.
Awake craniotomy

Objective: To report the personal experiences of patients undergoing awake craniotomy for brain tumor resection. Methods: We carried out a qualitative descriptive survey of patients’ experiences with awake craniotomies for brain tumor resection. The survey was conducted through a standard questionnaire form after the patient was discharged from the hospital. Results: Of the 9 patients who met the inclusion criteria and underwent awake craniotomy, 3 of those patients reported no recollection of the operation. Five patients had auditory recollections from the operation. Two-thirds (6/9) reported that they did not perceive pain. Five patients remembered the head clamp fixation, and 2 of those patients classified the pain from the clamp as moderate. None of the patients reported that the surgery was more difficult than anticipated. Conclusion: Awake craniotomy for surgical resection of brain tumors was well tolerated by patients. Most patients reported that they do not recall feeling pain during the operation. However, we feel that further work and exploration are needed in order to achieve better control of pain and discomfort during these types of operations.
4-DOF redundant haptic interface: Redundancy coordination method for control system design

The present work deals with the development of a 4-DOF redundant haptic interface, with particular focus on the problem of reaching the system's mechanical limits. After a brief presentation of the main characteristics of the device, of the kinematic structure of the mechanism and of the different methods used for the resolution of the inverse kinematics, an improvement of one of the methods is shown, together with results obtained from several simulations. Being the objective of the work just the definition of a redundancy coordination method, the system, rather than an haptic interface, has been analyzed as a parallel kinematic manipulator.
Accurate ECG R-peak detection for telemedicine

Electrocardiograms (ECGs) are usually recorded in a clinical setting by medical professionals using twelve leads attached to the patient. Our industry partner has developed a single-lead ECG machine for use by patients at home. Patients can then send these readings to remote doctors. The goal of the machines is to make medical expertise more accessible, affordable, and convenient. The ECGs recorded by patients with a single-lead suffer greatly from baseline wandering and high frequency noises, as compared to ECGs recorded with twelve-leads in a clinical setting. Accurate R-peak detection is an important step in ECG analysis. A variety of methods have been proposed in the past against standard clinical twelve-lead ECG recordings. In this study, we propose a new R-peak detection algorithm for single-lead mobile ECG recordings. Our area-based approach is built on the understanding that QRS complexes are typically narrow and tall, resulting in large areas over the curve around these locations. Our algorithm is simple to implement, computationally efficient, and does not require any signal pre-processing. This conceptual simplicity is a quality that distinguishes our approach from existing solutions. We evaluated our algorithm against data collected by patients from single-lead portable devices, and yielded 99.4% precision and 99.4% recall. The MIT/BIT Arrhythmia Database of twelve-lead clinical ECG recordings was also used to verify our algorithm. On this dataset we obtained a precision of 99.3% and recall of 98.6%.
Stochastic technical analysis for decision making on the financial market

We apply the well-known CUSUM and the Girshick-Rubin algorithm as trading strategies involving only mutually exclusive long positions in cash and the DAX at Frankfurt mid-day auction prices. We select optimal pairs of fixed thresholds for up- and down-movements from a pre-defined two-dimensional grid, hence, admitting asymmetric intervals. We show that under three different scenarios for transaction costs, the CUSUM technique not only outperforms the passive investment in the DAX but also the alternative Girshick-Rubin algorithm.
Transformer differential protection using positive sequence current; design and implementation

This paper describes the complete design of a prototype digital protective relay for three-phase transformers using positive sequence current. The major emphasis of the paper will be on the detailed description of the hardware and software of the prototype relay. The relay hardware consists of a data acquisition board and a microcomputer board which is based on the 80188 processor and input/output board. Sample real-time test cases are included in the paper. Performance studies results show that the proposed algorithm performs very well to recognize the various conditions in power transformers. The outstanding advantage of the proposed method with respect to the previous approaches, is requirement to less number of units for differential relay.