Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipidic Pore Formation by the Concerted Action of Proapoptotic BAX and tBID*

BCL-2 homology 3 (BH3)-only proteins of the BCL-2 family such as tBID and BIMEL assist BAX-type proteins to breach the permeability barrier of the outer mitochondrial membrane, thereby allowing cytoplasmic release of cytochrome c and other active inducers of cell death normally confined to the mitochondrial inter-membrane space. However, the exact mechanism by which tBID and BIMEL aid BAX and its close homologues in this mitochondrial protein release remains enigmatic. Here, using pure lipid vesicles, we provide evidence that tBID acts in concert with BAX to 1) form large membrane openings through both BH3-dependent and BH3-independent mechanisms, 2) cause lipid transbilayer movement concomitant with membrane permeabilization, and 3) disrupt the lipid bilayer structure of the membrane by promoting positive monolayer curvature stress. None of these effects were observed with BAX when BIMEL was substituted for tBID. Based on these data, we propose a novel model in which tBID assists BAX not only via protein-protein but also via protein-lipid interactions to form lipidic pore-type non-bilayer structures in the outer mitochondrial membrane through which intermembrane prodeath molecules exit mitochondria during apoptosis.
Motivations for Exercise and Weight Loss Among African-American Women: Focus group results and their contribution towards program development

Objective African-American women are more likely to be sedentary and maintain higher body weights compared with Caucasian women, although some are physically active and able to maintain weight loss. To develop effective intervention strategies, we need to understand why some women are successful. Design We conducted focus groups on four distinct groups of African-American women (currently physically active; currently sedentary; successful weight loss for S 1 year; unsuccessful weight loss) to explore motivations and intervention strategies. Open-ended questions, probes, and visual aids were used to stimulate discussions. Transcripts of sessions were read to highlight themes and concepts. Results Results indicated that motivators for the exercisers to start exercising were health concerns, weight control, stress reduction, and the influence of others. Motivators to continue exercising were feeling good and having energy. In contrast, the sedentary women reported that social support and enjoyment would be motivating. Both groups reported that physically active women conveyed the image of high energy and self-esteem. The successful weight loss women employed strategies that allowed them to eat a variety of foods and were less likely to 'diet'. The unsuccessful women referred to 'going on a diet' and were more likely to label foods as 'good' or 'bad'. They reported feeling tired and thought that losing weight would give them more energy. Conclusion This information was used to develop two culturally appropriate interventions for African-American women, which is presented. Conducting formative research in study design protocols can provide an important role in intervention development.
Estimating trends in the global mean temperature record

Given uncertainties in physical theory and numerical climate simulations, the historical temperature record is often used as a source of empirical information about climate change. Many historical trend analyses appear to deemphasize physical and statistical assumptions: examples include regression models that treat time rather than radiative forcing as the relevant covariate and time series methods that account for internal variability nonparametrically. However, given a limited record and the presence of internal variability, estimating radiatively forced historical temperature trends necessarily requires assumptions. Ostensibly empirical methods can involve an inherent conflict in assumptions: they require data records that are short enough for naive trend models to apply but long enough for internal variability to be accounted for. In the context of global mean temperatures, methods that deemphasize assumptions can therefore produce misleading inferences, because the twentieth century trend is complex and the scale of correlation is long relative to the data length. We illustrate how a simple but physically motivated trend model can provide better-fitting and more broadly applicable trend estimates and can address a wider array of questions. The model allows one to distinguish, within a single framework, between uncertainties in the shorter-term versus longer-term response to radiative forcing, with implications not only on historical trends but also on uncertainties in future projections. We also investigate the consequence on inferred uncertainties of the choice of a statistical description of internal variability. While nonparametric methods may seem to avoid making explicit assumptions, we demonstrate how even misspecified parametric methods, if attuned to important characteristics of internal variability, can result in more accurate statements about trend uncertainty.
Endoglycosidase and Glycoamidase Release of N‐Linked Oligosaccharides

Nearly all proteins entering the lumen of the endoplasmic reticulum (ER) become glycosylated en route to a cellular organelle, the plasma membrane, or the extracellular space. Many glycans can be attached to proteins, but the most common are the N‐linked oligosaccharides. These chains are added very soon after a protein enters the ER, but they undergo extensive remodeling (processing), especially in the Golgi. Processing changes the sensitivity of the N‐glycan to enzymes that cleave entire sugar chains or individual monosaccharides, which also changes the migration of the protein on SDS gels. These changes can be used to indicate when a protein has passed a particular subcellular location. This unit details some of the methods used to track a protein as it traffics from the ER to the Golgi toward its final location.
Influence of desorption and contact time on sediment‐water distribution of spiked polychlorinated biphenyls and polycyclic aromatic hydrocarbons: Relation with in situ distribution

The long‐term sediment—water distribution of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), spiked to Lake Ketelmeer (The Netherlands) sediment, was studied using a gas‐purge technique. Contact times varied from 2 to 1,461 d for the PCBs and from 5 to 100 d for the PAHs. Purge‐induced desorption experiments lasted 300 to <4,000 h. The initial distribution coefficients that were observed during the first part of the experiment were close to literature values for distribution after short contact times. The distribution coefficients increased during the purge‐induced desorption experiments. The final distribution coefficients that were observed during the last part of the experiment were one to two orders of magnitude higher than the initial values and were close to distribution coefficients reported earlier for in situ PCBs and PAHs present in a field‐contaminated sediment for years to decades. The change in distribution coefficients during a gas‐purge experiment may resemble the long‐term change in a field sediment. Final distribution coefficients seem to be a more relevant measure for the distribution coefficients of hydrophobic organic chemicals in aged field sediments than values obtained after short contact times.
Effect of alteration of caveolin‐1 expression on doxorubicin‐induced apoptosis in H9c2 cardiac cells

Doxorubicin is an anthracycline antibiotic widely used in cancer treatment. Although its antitumor efficacy appears to be dose dependent, its clinical use is greatly restricted by the development of cardiotoxicity associated with apoptosis. Although caveolin‐1, the major structural protein in caveolae, can positively or negatively regulate apoptosis depending on the stimulus or cell types, the contribution of caveolin‐1 to doxorubicin‐induced apoptosis remains unknown. This study was performed to identify the regulatory role of caveolin‐1 on doxorubicin‐induced apoptosis in H9c2 cardiac cells using a genetic approach. Caveolin‐1 knockdown with a short hairpin (sh) RNA adenovirus, but not overexpression of wild‐type caveolin‐1, resulted in a marked inhibition of doxorubicin‐induced caspase‐3 cleavage. However, caveolin‐1 knockdown tended to protect against doxorubicin‐induced decrease in cell viability, but it did not significantly reverse cell death induced by doxorubicin. Doxorubicin stimulated the phosphorylation of p38 and extracellular signal regulated kinase (ERK). Doxorubicin‐induced caspase‐3 cleavage was inhibited by U0126, a MEK inhibitor or SB203580, a p38 inhibitor. Caveolin‐1 knockdown markedly inhibited doxorubicin‐induced p‐38 phosphorylation but not ERK‐mediated p‐53 phosphorylation in H9c2 cardiac cells. Our results suggest that reduced caveolin‐1 expression plays an anti‐apoptotic role in doxorubicin‐induced apoptosis but that it is insufficient to prevent such an apoptosis in H9c2 cardiac cells.
Specific modulation of corticospinal and spinal excitabilities during maximal voluntary isometric, shortening and lengthening contractions in synergist muscles

Non‐technical summary The neural control of muscle activity differs during voluntary shortening and lengthening contractions. In this paper, we show that the relative contribution of both cortical and spinal mechanisms to the modulation of neural activation is specific during lengthening contraction and differs between synergist muscles. Knowledge of spinal and corticospinal excitabilities modulations during shortening and lengthening muscle contraction improves our understanding of the processes that underlies the neural control of muscles during dynamic contractions.
Quality of education and memory test performance in older men: the New York University Paragraph Recall Test normative data.

OBJECTIVES Memory evaluation is a key component in the accurate diagnosis of cognitive disorders.One memory procedure that has shown promise in discriminating disease-related cognitive decline from normal cognitive aging is the New York University Paragraph Recall Test; however, the effects of education have been unexamined as they pertain to one's literacy level. The current study provides normative data stratified by estimated quality of education as indexed by irregular word reading skill. METHOD Conventional norms were derived from a sample (N = 385) of cognitively intact elderly men who were initially recruited for participation in the PREADViSE clinical trial. A series of multiple linear regression models were constructed to assess the influence of demographic variables on mean NYU Paragraph Immediate and Delayed Recall scores. RESULTS Test version, assessment site, and estimated quality of education were significant predictors of performance on the NYU Paragraph Recall Test. Findings indicate that estimated quality of education is a better predictor of memory performance than ethnicity and years of total education. Normative data stratified according to estimated quality of education are presented. DISCUSSION The current study provides evidence and support for normativedata stratified by quality of education as opposed to years of education.
Dynamical Fluctuating Charge Force Fields: The Aqueous Solvation of Amides

The fluctuating charge (FQ) force field, a polarizable potential model in which point charges on atomic sites fluctuate in response to the environment, is applied to the aqueous solvation of acetamide and trans- and cis-N-methylacetamide (NMA). Two parameters are assigned to each kind of atom, corresponding to an electronegativity and a hardness. The FQ model accurately reproduces both the gas-phase and aqueous-phase charge distributions of these molecules and is therefore effective in treating the influence of functional group substitutions, conformation changes, and solvent on the charge distribution. The FQ model does this in a way that is computationally efficient by propagating the charges in time using an extended Lagrangian method. Solvation free energy calculations are done using both an explicit (FQ) solvent and a dielectric continuum solvent. Both solvent models predict a negligible free energy difference between trans- and cis-NMA, in agreement with experimental estimates. The explicit solvent .
Potential Clinical Use of the EDTA-Infusion Test

The introduction of assays for the intact parathyrin (parathyroid hormone) has dramatically improved the diagnosis and follow-up of patients with primary hyperparathyroidism. However, in some patients with mild or intermittent hypercalcaemia, when plasma concentrations of intact parathyrin may be within the normal reference concentrations, the diagnosis of primary hyperparathyroidism may still be problematic. In these patients, the EDTA-infusion test is of potential value, as it also might be in patients with equivocal operative findings.
Presenilin immunoreactivity in Alzheimer's disease

The role of presenilin (PS) mutations in familial Alzheimer's disease (AD) may be as a toxic gain of function, but in sporadic disease their contribution is more difficult to understand. In this study, we investigated PS proteins in sporadic AD by comparing the immunocytochemical profiles in sporadic AD with control brains using a quantitative immunocytochemical approach to both the N‐ and C‐terminals of PS1 and PS2. Ten patients with pathologically proven AD (using modified Consortium to Establish a Registry for Alzheimer's Disease [CERAD] criteria) and 10 controls were age‐ and sex‐matched. The immunocytochemical primary antibodies were affinity‐purified goat polyclonal antibodies and the secondary antibodies were biotinylated donkey anti‐goat to the N‐ and C‐terminal of both PS1 and PS2. The number of PS‐containing neurones was quantified manually and without the knowledge of the diagnosis. We found no significant differences in the number of PS1‐ and PS2‐containing neurones in three anatomical regions for both N‐ and C‐terminals between AD and controls. Our findings argue in favour of functional changes in PS molecules contributing to the pathogenesis of AD and are consistent with the hypothesis of dysfunction of the entire γ‐secretase complex, of which PS proteins are a constituent.
A Case Study of a Practitioner Researcher in Information Systems Development

Many key contributions to research in information systems development (ISD) have been made by practitioners. This exploratory study aims to advance the knowledge about practitioner researchers, which can help improve the cooperation between academics and practitioners in ISD research. Adopting a qualitative research strategy an exploratory case study of a practitioner researcher is carried out. The data is collected through an in-depth interview and a sample of refereed publications. The study shows that practitioner research is not limited to experience papers but includes theoretical contributions as well. Writing papers is how the practitioner researcher in the study reflects on his professional practice, and in this sense he writes them for himself. This may explain why he prefers theoretical papers, shows little interest in experience reports, does not document systematic data collection, and does not emphasise reflexivity in his papers.
On the transmission‐dominated to reprocessing‐dominated spectral state transitions in Seyfert 2 galaxies

We present Chandra and XMM-Newton observations of a small sample (11 objects) of optically selected Seyfert 2 galaxies, for which ASCA and BeppoSAX had suggested Compton-thick obscuration of the active galactic nucleus (AGN). The main goal of this study is to estimate the rate of transitions between 'transmission-dominated' and 'reprocessing-dominated' states. We discover one new transition in NGC 4939, with a possible additional candidate in NGC 5643. This indicates a typical occurrence rate of at least ∼0.02 yr -1 . These transitions could be due to large changes of the obscuring gas column density, or to a transient dimming of the AGN activity, the latter scenario being supported by detailed analysis of the best-studied events. Independently of the ultimate mechanism, comparison of the observed spectral dynamics with Monte Carlo simulations demonstrates that the obscuring gas is largely inhomogeneous, with multiple absorbing components possibly spread through the whole range of distances from the nucleus between a fraction of parsecs up to several hundred parsecs. As a by-product of this study, we report the first measurement ever of the column density covering the AGN in NGC 3393 (N H ≃ 4.4 x 10 24 cm -2 ), and the discovery of soft X-ray extended emission, apparently aligned along the host galaxy main axis in NGC 5005. The latter object most likely hosts an historically misclassified low-luminosity Compton-thin AGN.
Tympanometric Characteristics of Chinese School-aged Children

Objectives: To investigate the tympanometric characteristics of Chinese school-aged children with normal middle ear function. Design: Measurements were made for four tympanometric variables [peak, compensated static acoustic admittance (peak Ytm); equivalent ear canal volume (Vec); tympanometric width (TW); and tympanometric peak pressure] from 278 Chinese children aged between 6 and 15 yrs. Data from the right ear were compared across age groups with those of Chinese young adults and with Western children of comparable ages. Data from the left ear were used to examine specificity using tympanometric screening criteria suggested in the present study. Results: The developmental pattern in tympanometric variables found with the Chinese school-aged children in the study was similar to that found with white children in Western studies. Increasing age was accompanied by an increase in peak Ytm and Vec values, a decrease in TW values, and less negative and less varied tympanometric peak pressure values. The lower limit of peak Ytm 90% range of the Chinese school-aged children in the study was lower and their TW values were wider than those of white children. Age-specific data also suggested that the upper Vec limits of children between 6 and 7 yrs of age differed from those of older children. Racial differences in peak Ytm and TW values were noted, in that the Chinese school-aged children had a lower peak Ytm limit and wider TW values than white children. The use of ASHA 1997 guidelines for identifying ears for referral with respect to Chinese school-aged children may therefore not be highly sensitive and specific. Gender differences noted in peak Ytm and Vec values were too small to be of clinical significance. Conclusions: To increase the accuracy of tympanometry in determining ears to be referred for further assessment, the use of the tympanometric characteristics observed in the Chinese school-aged children in the present study (i.e., peak Ytm lower limit <0.2 mmhos and Vec upper limit >1.5 cm3) should be considered in addition to ASHA 1997 tympanometric screening guidelines.
Ice surfaces: macroscopic effects of microscopic structure

The balance between ice and water controls the habitability of an important fraction of the globe and influences the majority of the world'population. The freezing of water to form ice is one of the most common phase transformations in the natural environment. However, a complete understanding of its microscopics and their influence on macroscopic phenomena still eludes us. As this millennium comes to a close, we are beginning to understand how the microscopic interfacial structure of ice controls pattern formation during ice–crystal growth, the evolution of the polycrystalline fabrics of the great ice sheets, the dynamics of ground freezing, ozone destruction, and the mechanism of charge transfer that drives thunderstorm electrification. This paper describes our evolving understanding, its implications for the basic principles of melting and freezing, and their environmental consequences.
Development of Adrenergic and Cholinergic Cardiac Control in Larvae of the African Clawed Frog Xenopus laevis

Cardiac responses (heart rate, stroke volume, and cardiac output) to cholinergic and adrenergic receptor stimulation were investigated in developing larvae of Xenopus laevis from Nieuwkoop and Faber (NF) stage 33/34 (newly hatched) to NF stage 53 (22 d after hatching). Effects on heart rate (fH), stroke volume (SV), and cardiac output (CO) were analyzed using in situ preparations and video‐microscopic techniques to record the continually beating heart. The results show that administration of acetylcholine to the heart decreases heart rate as early as NF stage 40. A significant reduction in SV and CO following acetylcholine administration to the heart was found at NF stages 45–53. Epinephrine had no significant effect on fH, SV, or CO at any of the stages investigated. However, an adrenergic tonus on the heart is present already at NF stage 40 (11%). This tonus increases up to a maximum (44%) at NF stages 45–47, when the maximal heart rate is found during development of X. laevis. We conclude that acetylcholine has a negative chronotropic and possibly also inotropic effect on the heart very early in development of X. laevis. We also hypothesize that the high adrenergic tonus found at NF stages 45–47 is responsible, at least in part, for the peak in heart rate seen at these stages.
Stem Lagomorpha and the Antiquity of Glires

We describe several fossils referable to Gomphos elkema from deposits close to the Paleocene-Eocene boundary at Tsagan Khushu, Mongolia. Gomphos shares a suite of cranioskeletal characters with extant rabbits, hares, and pikas but retains a primitive dentition and jaw compared to its modern relatives. Phylogenetic analysis supports the position of Gomphos as a stem lagomorph and excludes Cretaceous taxa from the crown radiation of placental mammals. Our results support the hypothesis that rodents and lagomorphs radiated during the Cenozoic and diverged from other placental mammals close to the Cretaceous-Tertiary boundary.
D‐myo‐inositol derivatives alter liposomal membrane fluidity

We investigated the effect on membrane fluidity induced by D‐myo‐inositol derivatives (IP3, IP4, IP5, IP6). Fluidity was determined as the anisotropy of fluorescence polarisation from liposome model membranes labelled with DPH (1,6‐diphenyl‐1,3,5 hexatriene). IP3 (10‐10 to 10‐5 M) increased the membrane fluidity with a maximum effect at 10‐5 M. For IP4, IP5 and IP6, at concentrations less than 10‐6 M these derivatives increased the membrane viscosity (i.e. reduced fluidity). This effect was enhanced when the derivatives were incorporated in the vesicles, rather than added to the vesicle suspension. In this case IP5 and IP6 increased viscosity over the reference values. We conclude that inositol derivatives directly modified membrane fluidity which could play a role in their effects in biological systems, beside the one mediated by binding to specific receptors.