Miracle-dz/UniFAR-FTUs huggingface dataset:
Essential Roles for Fe65, Alzheimer Amyloid Precursor-binding Protein, in the Cellular Response to DNA Damage*

Fe65 interacts with the cytosolic domain of the Alzheimer amyloid precursor protein (APP). The functions of the Fe65 are still unknown. To address this point we generated Fe65 knockout (KO) mice. These mice do not show any obvious phenotype; however, when fibroblasts (mouse embryonic fibroblasts), isolated from Fe65 KO embryos, were exposed to low doses of DNA damaging agents, such as etoposide or H2O2, an increased sensitivity to genotoxic stress, compared with wild type animals, clearly emerged. Accordingly, brain extracts from Fe65 KO mice, exposed to non-lethal doses of ionizing radiations, showed high levels of γ-H2AX and p53, thus demonstrating a higher sensitivity to X-rays than wild type mice. Nuclear Fe65 is necessary to rescue the observed phenotype, and few minutes after the exposure of MEFs to DNA damaging agents, Fe65 undergoes phosphorylation in the nucleus. With a similar timing, the proteolytic processing of APP is rapidly affected by the genotoxic stress: in fact, the cleavage of the APP COOH-terminal fragments by γ-secretase is induced soon after the exposure of cells to etoposide, in a Fe65-dependent manner. These results demonstrate that Fe65 plays an essential role in the response of the cells to DNA damage.
Heuristic evaluation of healthy menus: examining the effect of brand image congruity

Purpose This study aims to investigate how restaurant customers’ heuristic judgment, originating from their perceived level of congruity between restaurant brand image regarding healthfulness and healthy menu products, can affect their information processing in terms of their perceived nutritional information credibility and, furthermore, how these effects influence customers’ attitude toward the menu in terms of healthiness. Design/methodology/approach A Web-based survey was developed and distributed to randomly selected respondents in the USA, and in total, 320 responses were used for the data analyses. Structural equation modeling (SEM) was used to examine the relationship among three constructs: perceived brand–product congruity, perceived nutritional information credibility and nutrition attitude toward the healthy menu item being promoted. To assess the mediating role of perceived information credibility, an analytical procedure proposed by (Baron and Kenny 1986) was used. Finally, to investigate the moderating effect of the health involvement, multiple group analyses were executed. Findings The study results suggested that the synchronization between healthful brand image of the restaurant and the promoted menu item is important for ensuring customers’ perceptions of information credibility regarding the menu item healthiness and for eliciting customers’ positive nutrition attitudes toward the menu item. Also, positive nutrition attitudes toward a menu item can be increased by improving perceived information credibility. Depending on an individual’s level of health involvement, the relationships between the three proposed constructs vary. Originality/value This paper includes a theoretical model that explains customers’ heuristic evaluation of a healthy menu product by assessing the influence of brand image congruity in terms of healthy menu promotion.
Discretionary Fiscal Policy in the Euro Area: Past, Present and Future

During the years of the so-called "Great Moderation", monetary policy and automatic stabilizers were deemed sufficient for counter-cyclical purposes. However, the depth and the length of the recent crisis, together with policy interest rates at the zero lower bound, induced a more positive re-assessment of a countercyclical fiscal stance, especially in the euro area. Against this background, we look at discretionary fiscal policy in the euro area from three different perspectives. First, we provide evidence that the discretionary fiscal policy in euro area countries has been mostly acyclical even if our estimates suggest that it could have been useful, particularly during the crisis. Second, focusing on the short-run - i.e. taking as given the economic and institutional constraints that currently make a significant fiscal expansion quite unrealistic in Europe - we discuss some budget-neutral proposals aimed at fostering economic growth. Finally, taking a more forward-looking perspective, we discuss the issue of the appropriate fiscal stance for the euro area as a whole, and argue that the advantages of having a coordinated approach (e.g. through a fiscal capacity at the central level) can be substantial.
Absence of mutations in the granulocyte colony‐stimulating factor (G‐CSF) receptor gene in patients with myelodysplastic syndrome/acute myeloblastic leukaemia occurring after treatment of aplastic anaemia with G‐CSF

The development of myelodysplastic syndrome/acute myeloblastic leukaemia (MDS/AML) has been reported in patients with aplastic anaemia (AA) after administration of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF). Similarly, patients with severe congenital neutropenia (SCN) have an increased risk of developing MDS/AML after treatment with rhG‐CSF. Point mutations in the G‐CSF receptor gene are found in about 20% of SCN patients who are predisposed to MDS/AML. We investigated the occurrence of mutations in the G‐CSF receptor in eight patients with AA who developed MDS/AML. No mutations were detected around the cytoplasmic domain of the gene in our patients, indicating that the mechanisms of clonal evolution to MDS/AML in patients with AA might be different from those with SCN.
Peritoneal Loss of Growth Hormone in Children on Automated Peritoneal Dialysis

Objective To provide quantitative data regarding the daily dialytic loss of growth hormone (GH) in children on peritoneal dialysis (PD). Design Prospective study involving 24-hour dialysate collections on 3 consecutive days in patients with and without recombinant human GH (rhGH) treatment. Setting Single-center outpatient PD program. Patients Twenty-six children undergoing automated PD (APD): 6 with and 20 without daily rhGH. Main Outcome Measures Daily peritoneal losses of GH, α1-, β2-microglobulin, transferrin, and albumin. Results The mean (±SEM) daily dialytic GH loss was 2.18 ± 0.62 μg/1.73 m2 per day in rhGH-treated patients and 0.42 ± 0.28 μg/1.73 m2 per day in untreated patients, (p < 0.05). The intraindividual coefficient of variation of daily GH loss was 65%. The peritoneal loss of GH was positively correlated with that of β2-microglobulin (r = 0.77, p < 0.001) and α1-microglobulin (r = 0.51, p < 0.01). The variability in β2-microglobulin and α1-microglobulin elimination, together with the use of rhGH, explained 66% of the total variability of daily GH excretion. In patients without rhGH therapy, the daily peritoneal GH loss was approximately 0.05% of the estimated daily endogenous production rate based on previous estimates in children with end-stage renal failure. In patients on rhGH therapy, less than 0.1% of the injected rhGH dose was eliminated by dialysis. Conclusion Peritoneal losses of GH in children on APD account only for a minute fraction of endogenous metabolic clearance, and do not explain the variability of the rhGH treatment response. The assessment of dialytic GH elimination may be used to estimate time-integrated mean plasma GH concentrations, and to monitor rhGH treatment compliance.
On the Validity of the Beck Depression Inventory

The present review discusses validity aspects of the Beck Depression Inventory (BDI) on the basis of meta-analyses of studies on the psychometric properties. Shortcomings of the BDI are its high item difficulty, lack of representative norms, and thus doubtful objectivity of interpretation, controversial factorial validity, instability of scores over short time intervals (over the course of 1 day), and poor discriminant validity against anxiety. Advantages of the inventory are its high internal consistency, high content validity, validity in differentiating between depressed and nondepressed subjects, sensitivity to change, and international propagation. The present paper outlines agreements and contradictions between the various studies on the BDI and discusses the potential factors (composition of the subject sample, statistical procedures, point in time of measurement) accounting for the variance in their results.
A Multiobjective Evolutionary Algorithm That Diversifies Population by Its Density

Most existing multiobjective evolutionary algorithms (MOEAs) assume the existence of Pareto-optimal solutions/Pareto-optimal objective vectors in a neighborhood of an obtained Pareto-optimal set (PS)/Pareto-optimal front (PF). Obviously, this assumption does not work well on the multiobjective problem (MOP) whose true PF and true PS are in the form of multiple segments-truly disconnected MOP (TYD-MOP). Moreover, these MOEAs commonly involve more than three control parameters; and some of them even involve nine control parameters. The stabilities of their performance against parameter settings are generally unknown. In this paper, we propose a MOEA, namely multiobjective density driven evolutionary algorithm (MODdEA), which can handle TYD-MOP. MODdEA stores all evaluated solutions by a binary space partitioning (BSP) tree. Benefiting from the BSP scheme, a fast solution density estimation by the archive is naturally obtained. MODdEA uses this estimated density together with the nondominated rank to probabilistically select mating individuals, which relaxes the neighborhood assumption on PF in a parameter-less manner. Moreover, two genetic operators, extended arithmetic crossover and diversified mutation, are proposed to enhance the explorative search ability of the algorithm. MODdEA is examined on two test problem sets. The first test set consists of six TYD-MOPs; the second test set consists of 17 benchmark MOPs which are commonly examined by the existing MOEAs. Comparing to 14 test MOEAs, MODdEA has superior performance on TYD-MOP and is competitive on MOP whose true PF and PS are one single connected segment.
Performance study for an acoustic-inertial close range navigation system used in minimally-invasive surgical interventions

The present contribution is concerned with the design of a 3D real-time navigation system for minimally-invasive surgical interventions. We employ an absolute positioning system based on short range acoustic positioning technology together with an inertial navigation system. Both of the signals are fused using hybrid extended Kalman filtering in order to obtain a precise pose estimation of the surgical instrument. Simulation studies provide specification of the demands for the acoustic sensor system and the margins of usability for such a surgical navigation system.
Spondyloepimetaphyseal dysplasia with joint laxity (Beighton type); mutation analysis in eight affected South African families

Spondyloepimetaphyseal dysplasia with joint laxity (SEMD‐JL), type 1 is an autosomal recessive disorder which has been identified in more than 30 affected children in the Afrikaans‐speaking community of South Africa. Sequencing of B3GALT6 revealed a specific mutation, c.235A > G, in homozygous form in four families, while three others were compound heterozygotes for this mutation in combination with the c.200C > T mutation. In addition, a proband from one family carried the c.16C > T mutation combined with c.200C > T. In a series of five Iranian persons, mutations in B3GALT6 have been implicated in a syndrome characterised by skeletal abnormalities with intellectual disability, bone and connective tissue fragility. Other mutations in B3GALT6 resulted in the classical SEMD‐JL phenotype in seven Japanese families and in a syndrome which has been likened to a progeroid form of Ehlers–Danlos syndrome (EDS). It is evident that there is considerable intragenic heterogeneity in B3GALT6. One of the mutations, c.200C > T, in the affected South Africans was also present in one of the Japanese persons and the respective phenotypes were identical. The multiplicity of allelic mutations and the phenotypic differences in the affected persons supports the concept that a spectrum of connective tissue disorders is programmed by mutations in B3GALT6.
Analytical model for out-of-field dose in photon craniospinal irradiation

The prediction of late effects after radiotherapy in organs outside a treatment field requires accurate estimations of out-of-field dose. However, out-of-field dose is not calculated accurately by commercial treatment planning systems (TPSs). The purpose of this study was to develop and test an analytical model for out-of-field dose during craniospinal irradiation (CSI) from photon beams produced by a linear accelerator. In two separate evaluations of the model, we measured absorbed dose for a 6 MV CSI using thermoluminescent dosimeters placed throughout an anthropomorphic phantom and fit the measured data to an analytical model of absorbed dose versus distance outside of the composite field edge. These measurements were performed in two separate clinics—the University of Texas MD Anderson Cancer Center (MD Anderson) and the American University of Beirut Medical Center (AUBMC)—using the same phantom but different linear accelerators and TPSs commissioned for patient treatments. The measurement at AUBMC also included in-field locations. Measured dose values were compared to those predicted by TPSs and parameters were fit to the model in each setting. In each clinic, 95% of the measured data were contained within a factor of 0.2 and one root mean square deviation of the model-based values. The root mean square deviations of the mathematical model were 0.91 cGy Gy−1 and 1.67 cGy Gy−1 in the MD Anderson and AUBMC clinics, respectively. The TPS predictions agreed poorly with measurements in regions of sharp dose gradient, e.g., near the field edge. At distances greater than 1 cm from the field edge, the TPS underestimated the dose by an average of 14% ± 24% and 44% ± 19% in the MD Anderson and AUBMC clinics, respectively. The in-field measured dose values of the measurement at AUBMC matched the dose values calculated by the TPS to within 2%. Dose algorithms in TPSs systematically underestimated the actual out-of-field dose. Therefore, it is important to use an improved model based on measurements when estimating out-of-field dose. The model proposed in this study performed well for this purpose in two clinics and may be applicable in other clinics with similar treatment field configurations.
Creative hybridity over linguistic purity: the status of English in the United Arab Emirates

Abstract Currently, the linguistic landscape in the United Arab Emirates (UAE) can be described as dynamic, complex and multifaceted. This article discusses the status of English in the UAE with three key periods of language change being identified, based on Schneider’s ‘dynamic model’ of postcolonial Englishes. The increasing impact of English as a lingua franca, and the recent shift towards English Medium Instruction at all levels of Emirati education are then explored before examining attitudes towards English with reference to the ‘Englishization vs. hybridization’ debate. It is argued that rather than English and Arabic being used in a binary way representing linguistic purity, the UAE’s linguistic landscape is more complex and dynamic. Emiratis are increasingly using multiple forms of linguistic hybridity such as ‘white dialects’, ‘Arabizi’, ‘translanguaging’ and ‘code-switching’, which are reshaping Emirati language use and additionally influencing local identities.
MicroRNA-222 promotes the proliferation and migration of cervical cancer cells.

PURPOSE This study aimed to investigate the role of small non-coding RNA-222 (microRNA-222; miR-222) in the development of cervical cancer (CC). METHODS Normal and CC specimens were obtained from 18 patients. HeLa and SiHa cells were grown in Dulbecco's modified Eagle's medium. RT-PCR, Western blot, migration assay, flow cytometry and immunofluorescence microscopy were used for analyses. RESULTS When compared with normal cervical tissues, miR-222 was upregulated in human CC, and the extent of up-regulation was associated with the extent and depth of CC invasion. Expression of miR-222 was inversely related to the expression of phosphatase and tensin homolog (PTEN) and p27. The reduced the expression of PTEN and p27 by miR-222 in HeLa cells and SiHa cells was associated with increased proliferation and migration of CC cells. The expression of proteins (E-cadherin and paxillin) related to the proliferation and migration was also elevated. CONCLUSION MiR-222 plays an important role in the tumorigenesis of CC, possibly by specifically down-regulating p27Kip1 and PTEN. Our findings suggest that miR-222 may serve as a new therapeutic target in CC.
Angiotensin converting enzyme inhibitors and pulmonary hypertension.

AIM To evaluate the efficacy of angiotensin converting enzyme inhibitors Enalapril, Fosonopril and Moexipril on mean and systolic pulmonary artery pressure. MATERIAL AND METHODS The study included Ill patients with chronic obstructive bronchopneumopathies associated with arterial hypertension and mild to moderate heart failure (NYHA I-II class). The patients were examined at baseline and after 60 days of treatment. The central hemodynamic parameters and mean and systolic pulmonary artery pressure were studied by Doppler echocardiography (Phillips HD11XE). The pulmonary artery was viewed by left parasternal approach - cross section of the aorta. The following were measured: pulmonary artery flow acceleration and deceleration time (pafAT/ pafDT), right ventricular izovolumetric relaxation time (IVRT), mean and peak pulmonary blood flow velocities, right ventricular/pulmonary artery systolic pressure (RV/ PASP). The mean pulmonary artery pressure (MPAP) was estimated based on pulmonary flow acceleration time and right ventricular ejection time. RESULTS Following the treatment with angiotensin converting enzyme inhibitors a positive dynamics of SF pattern close to the normal one - a domelike contour with the maximum almost in the middle of diastole was noticed. CONCLUSIONS the quantitative estimation revealed the considerable reduction in pulmonary artery systolic pressure (PASP) (from 46.3 +/- 3.3 mmHg at baseline to 32.1 +/- 2.6 mmHg after treatment, p < 0.01) and MPAP - from 26.7 +/- 3.2 mmHg at baseline to 23.2 +/- 2.6 mmHg after treatment, p
Factors associated with long-term institutionalization of older people with dementia: data from the Canadian Study of Health and Aging.

BACKGROUND In Canada, half the people with dementia live in institutions. Factors associated with institutionalization should be identified with the goal of implementing strategies not only to permit those with dementia to stay in their homes as long as is feasible but also to ensure that steps are taken for timely institutionalization when appropriate. METHODS Informal caregivers of 326 individuals with dementia living in the community were identified and interviewed as part of the Canadian Study of Health and Aging (CSHA). These subjects were contacted again 2.5 and 5 years after the baseline interview to collect information on the status of their care recipients. Survival analyses using clinical data for the individuals with dementia and data from the interviews with their informal caregivers were carried out using Cox proportional hazard modeling to estimate the hazard ratio (HR). RESULTS Over the 5-year period, 166 individuals with dementia (50.9%) were institutionalized and the median time to admission was 41 months. From the multivariate analysis, the factors significantly associated with institutionalization were: type of dementia (Alzheimer's disease: HR = 1.83), severity of disability (mild: 1.51; moderate: 2.34; total impairment: 4.02), caregiver's age over 60 (1.83), caregiver not a spouse or child (1.55), and severe caregiver burden (1.71). Caregiver's burden was associated with the care-receiver's behavioral disturbance (partial r =.55) and the caregiver's depressive mood (r =.55). CONCLUSIONS Screening caregivers for burden and depression and designing interventions to decrease the consequences of behavioral disturbance on caregivers would be relevant avenues to explore to decrease institutionalization of people with dementia.
An Atypical KdpD Homologue from the Cyanobacterium Anabaena sp. Strain L-31: Cloning, In Vivo Expression, and Interaction with Escherichia coli KdpD-CTD

ABSTRACT The kdpFABC operon of Escherichia coli, coding for the high-affinity K+ transport system KdpFABC, is transcriptionally regulated by the products of the adjacently located kdpDE genes. The KdpD protein is a membrane-bound sensor kinase consisting of a large N-terminal domain and a C-terminal transmitter domain interconnected by four transmembrane segments (the transmembrane segments together with the C-terminal transmitter domain of KdpD are referred to as CTD), while KdpE is a cytosolic response regulator. We have cloned and sequenced the kdp operon from a nitrogen-fixing, filamentous cyanobacterium, Anabaena sp. strain L-31 (GenBank accession. number AF213466 ). The kdpABC genes are similar in size to those of E. coli, but the kdpD gene is short (coding only for 365 amino acids), showing homology only to the N-terminal domain of E. coli KdpD. A kdpE-like gene is absent in the vicinity of this operon. Anabaena KdpD with six C-terminal histidines was overproduced in E. coli and purified by Ni2+-nitrilotriacetic acid affinity chromatography. With antisera raised against the purified Anabaena KdpD, the protein was detected in Anabaena sp. strain L-31 membranes. The membrane-associated or soluble form of the Anabaena KdpD(6His) could be photoaffinity labeled with the ATP analog 8-azido-ATP, indicating the presence of an ATP binding site. The coproduction of Anabaena KdpD with E. coli KdpD-CTD decreased E. coli kdpFABC expression in response to K+ limitation in vivo relative to the wild-type KdpD-CTD protein. In vitro experiments revealed that the kinase activity of the E. coli KdpD-CTD was unaffected, but its phosphatase activity increased in the presence of Anabaena KdpD(6His). To our knowledge this is the first report where a heterologous N-terminal domain (Anabaena KdpD) is shown to affect in trans KdpD-CTD (E. coli) activity, which is just opposite to that observed for the KdpD-N-terminal domain of E. coli.
Organisational culture and the implementation of Six Sigma in Southern China

Six Sigma has become increasingly common in China, where the typical management practices are substantially different from those in the US, the original location of Six Sigma. Based upon existing organisational change research, this raises questions as to whether the existing management culture in Chinese organisations influences the success of Six Sigma implementations. This paper demonstrates that the existing organisational culture does have an influence upon Six Sigma implementation within China. In particular, organisations with a Supportive Culture appear more likely to report success, while organisations with an Innovation Culture surprisingly appear to experience difficulties implementing Six Sigma. Additionally, having clear objectives at the start of the project is critical to ultimate Six Sigma implementation success.