Miracle-dz/UniFAR-FTUs huggingface dataset:
MAP kinase-mediated phosphorylation of distinct pools of histone H3 at S10 or S28 via mitogen- and stress-activated kinase 1/2

ERK and p38 MAP kinases, acting through the downstream mitogen- and stress-activated kinase 1/2 (MSK1/2), elicit histone H3 phosphorylation on a subfraction of nucleosomes – including those at Fos and Jun – concomitant with gene induction. S10 and S28 on the H3 tail have both been shown to be phospho-acceptors in vivo. Both phospho-epitopes appear with similar time-courses and both occur on H3 tails that are highly sensitive to TSA-induced hyperacetylation, similarities which might suggest that MSK1/2 phosphorylates both sites on the same H3 tails. Indeed, on recombinant histone octamers in vitro, MSK1 efficiently phosphorylates both sites on the same H3 tail. However, sequential immunoprecipitation studies show that antibodies against phosphorylated S10-H3 recover virtually all this epitope without depletion of phosphorylated S28-H3, and vice versa, indicating that the two phospho-epitopes are not located on the same H3 tail in vivo. Confocal immunocytochemistry confirms the clear physical separation of the two phospho-epitopes in the intact mouse nucleus. Finally, we used transfection-based experiments to test models that might explain such differential targeting. Overexpression and delocalisation of MSK1 does not result in the breakdown of targeting in vivo despite the fact that the ectopic kinase is fully activated by external stimuli. These studies reveal a remarkable level of targeting of S10 and S28 phosphorylation to distinct H3 tails within chromatin in the interphase mouse nucleus. Possible models for such exquisite targeting are discussed.
Diagnosis of cystic fibrosis related diabetes: a selective approach in performing the oral glucose tolerance test based on a combination of clinical and biochemical criteria

BACKGROUND Cystic fibrosis related diabetes (CFRD) has become increasingly common with the increasing longevity of patients with cystic fibrosis. The diagnosis of CFRD is important as its development may lead to a clinical deterioration which may be reversed with treatment. The oral glucose tolerance test (OGTT) is the method of choice in the diagnosis of CFRD, but performing OGTTs on all patients is inconvenient for patients and labour intensive for staff. The aim of this study was to identify a more selective approach in performing OGTTs in the diagnosis of CFRD based on the use of a combination of clinical and biochemical criteria. METHODS Clinically stable adult patients with cystic fibrosis not known to be diabetic attending the Royal Brompton Hospital Cystic Fibrosis Clinic for their annual review were invited to return within a month to have an OGTT. The result of the OGTT was compared with the results of tests performed during the annual review. The sensitivities and specificities of various methods used in the screening or diagnosis of CFRD were determined using OGTT as the “gold standard” diagnostic method. The combination of clinical and biochemical criteria which resulted in the highest sensitivity and specificity in the diagnosis of CFRD was determined. RESULTS Between August 1996 and May 1997 122 patients became eligible for the study, 91 of whom agreed to take part. The number of patients with normal, impaired, and diabetic glucose tolerance was 58 (64%), 21 (23%), and 12 (13%), respectively. When used alone, abnormal glycosylated haemoglobin (HbA1c) was found to have the highest sensitivity (83%; 95% CI 62 to 100) in the diagnosis of CFRD. The combination of an abnormal random blood glucose and/or abnormal HbA1c and/or symptoms of hyperglycaemia or weight loss was found to have the highest sensitivity (92%; 95% CI 76 to 100) in the diagnosis of CFRD. The specificity of this combination in the diagnosis of CFRD was 79% (95% CI 70 to 88). By selectively performing OGTTs in patients with one or more of the criteria cited above, 11 of the 12 patients with OGTT defined diabetes would have been identified. CONCLUSIONS Patients with cystic fibrosis already have to undergo a large number of routine investigations. The selective approach in performing OGTTs described here has the potential to identify the majority of patients with CFRD without the need to perform this investigation on all patients. This approach is likely to be welcomed by patients and will lead to significant savings in terms of time and resources for patients and staff. Further larger studies are warranted to validate this selective approach in the diagnosis of CFRD.
Opus: University of Bath Online Publication Store Pain-specific Modulation of Hippocampal Activity and Functional Connectivity during Visual Encoding

(2013) Pain-specific modulation of hippocampal activity and functional connectivity during visual encoding. This version is made available in accordance with publisher policies. Please cite only the published version using the reference above. Acute and chronic pain automatically attract attention and thus interfere with cognitive functioning. Impaired memory is a prominent complaint of patients with chronic pain that substantially contributes to pain-related disability. In this fMRI study, we investigated the specific influence of pain on neural processes of memory encoding in healthy human volunteers using a visual task. To investigate the specificity of the interruptive effect of pain on the encoding of visual objects, objects were presented (1) alone, (2) with painful heat stimuli, or (3) with auditory stimuli that were matched for unpleasantness to the heat stimuli. The interruptive effect of concomitant aversive stimulation on behavioral measures and neural processing was assessed in a categorization task during encoding and in a subsequent recognition task. Pain interfered with object processing and encoding of visual stimuli. On the behavioral level, this resulted in slower reaction times during the categorization task for pain compared with auditory stimuli and in a lower recognition rate in the pain condition but not in the tone condition. Pain catastrophizing amplified this interruptive effect of pain. On the neural level, this pain-related disruption of encoding was associated with reduced activity in the right anterior hippocampus during encoding. Moreover, the hippocampus exhibited reduced functional connectivity with extrastriate regions during painful stimulation relative to auditory stimulation. In summary, our results show a pain-related disruption of visual encoding over and above the unpleasantness of a stimulus, suggesting a pain-specific interruptive mechanism that interferes with an early stage of memory formation.
Determinants of driving under the influence of alcohol or drugs among latino immigrants in miami-dade county, florida

ABSTRACT Little is known about the pre- and postimmigration drinking and drunk- and drugged-driving behavior of Latino immigrants. Despite showing risky drinking behaviors, many recent immigrants of low socioeconomic status (SES) do not drive while impaired by alcohol (DWI) due largely to limited access to a vehicle. This effort examines the DWI and driving while impaired by drugs (DWID) behaviors of Latino immigrants who have access to a vehicle. Data came from an ongoing longitudinal sample of Latino immigrants to Miami-Dade County, Florida. Bivariate analyses and logistic regression were applied. Preimmigration DWI and DWID was the best predictor of postimmigration DWI and DWID. Future interventions should make efforts to (a) identify immigrants who had DWI and DWID in their country of origin and (b) design and deliver specific and culturally relevant messages to persuade them not to engage in DWI and DWID after immigration.
Molecular Mechanism of Basal CYP3A4 Regulation by Hepatocyte Nuclear Factor 4α: Evidence for Direct Regulation in the Intestine

Cytochrome P450 3A4 plays an outstanding role in the metabolism of clinically used drugs and shows a marked interindividual variability in expression even in the absence of inducing agents. Thus, regulation of basal expression contributes considerably to variability. The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) was previously shown to be associated with basal hepatic CYP3A4 expression. As how HNF4α regulates basal expression of CYP3A4 still remains elusive, we systematically screened 12.5 kilobase pairs (kb) of the CYP3A4 5′ upstream region for activation by the receptor in the human intestinal cell line LS174T. In this study, we newly identified two widely separated regions mediating the activation by HNF4α: a far distal region at -9.0 kb and the proximal promoter region at ∼-0.2 kb. By gel shift experiments and transient transfections, we characterized direct repeat (DR) 1-type motifs in both regions as functional HNF4α response elements. Cooperation of the two regions was shown to be required for maximal activation by HNF4α. The effect of HNF4α was antagonized by chicken ovalbumin upstream promoter transcription factor II, which was shown to bind to one of the DR1 motifs. Furthermore, activation of CYP3A4 via the DR1 element in the proximal promoter depends on an additional, yet unknown, factor, which is binding at ∼-189 base pairs. Physiological relevance of this position for activation by HNF4α in vivo is suggested by the presence of a binding activity in small intestine similar to that in LS174T cells. In summary, we here have elucidated a molecular mechanism of direct regulation of CYP3A4 by HNF4α, which is probably specific for the intestine.
Treasury Inflation-Indexed Debt: A Review of the U.S. Experience

This article describes the evolution of Treasury inflation-indexed debt securities (TIIS) since their introduction in 1997. Over most of this period, TIIS yields have been surprisingly high relative to those on comparable nominal Treasury securities, with the spread between the nominal and indexed yields falling well below survey measures of long-run inflation expectations. The authors argue that the low relative valuation of TIIS may have reflected investor difficulty adjusting to a new asset class, supply trends, and the lower liquidity of indexed debt. In addition, investors may have had a benign outlook for inflation and may not have demanded much, if any, of an inflation risk premium to hold nominal securities. As a result, inflation-indexed debt has not yet lived up to one of its main purposes: to reduce the Treasury's expected financing costs. More recently, though, TIIS market liquidity and the breadth of investor participation have increased considerably, and the valuation of these securities appears to have improved.
Studies on the mechanism of solubilization of immune precipitates by serum

Antigen (Ag)-antibody (Ab) aggregates prepared with several different antigens are solubilized by fresh serum at 37 degrees C (complex- release activity of serum or CRA). The rate of solubilization varies in different systems and is strongly influenced by the affinity of Ab for the Ag in the immune precipitate. With a given Ag-Ab precipitate, the maximum amount of complex that can be solubilized by individual sera is independent of the initial concentration of complexes and cannot be increased by prolonged incubation. CRA occurs in the absence of C2 and C4, but not in the absence of C3 and factor B of the properdin pathway. Addition of C2 to C2-deficient serum or C4 to C4-deficient serum enhances CRA. Solubilization does not involve extensive degradation of the complexed antibody, as might be detected by acrylamide gel electrophoresis of released antibody after reduction and alkylation to separate H and L chains. Immune precipitates can also be solubilized by incubation with monovalent fragments (Fab or Fab') of antibodies against determinants of the Ab molecules in the immune precipitate. In contrast, F(ab')2 fragments decrease the solubility of the immune precipitates. In view of these findings, we propose that CRA is mediated by the binding of functionally monovalent C fragments (C3 and C4) onto Ab molecules in the precipitates.
H3PO4-Activated Cattail Carbon Production and Application in Chromium Removal from Aqueous Solution: Process Optimization and Removal Mechanism

In this study, Box–Behnken design (BBD) was employed to optimize the process for H3PO4-activated Typha angustifolia activated carbon (TAC) production and Cr removal by TAC; the removal mechanisms were discussed based on TAC characterization, and the regeneration evaluation was also conducted. The optimum preparation conditions were activated time of 1.5 h, temperature of 469.02 °C, and incubation ratio of 4, resulting in an experimental carbon yield of 38.23% and Cr removal of 90.01%. The optimum adsorption parameters were found to be 0.02 g/50 mL TAC, 80 mg/L Cr(VI), and 2.21 pH with the observed Cr adsorption capacity of 59.54 mg/g. The removal mechanisms involved coulombic attraction, ionic exchange, surface complexation, and reduction. The process of Cr(VI) adsorption was feasible, spontaneous, and endothermic in nature, and the pseudo-second-order and Langmuir isotherm models were more appropriate for the removal process. After five adsorption/desorption cycles, the Cr adsorption capacity on TAC reduced by only 24.37%. The results showed that BBD could successfully optimize TAC production and Cr removal, and TAC could be developed as a promising, eco-friendly, and effective adsorbent for Cr pollution control.
Increases in air temperature can promote wind-driven dispersal and spread of plants

Long-distance dispersal (LDD) of seeds and pollen shapes the spatial dynamics of plant genotypes, populations and communities. Quantifying LDD is thus important for predicting the future dynamics of plants exposed to environmental changes. However, environmental changes can also alter the behaviour of LDD vectors: for instance, increasing air temperature may enhance atmospheric instability, thereby altering the turbulent airflow that transports seed and pollen. Here, we investigate temperature effects on wind dispersal in a boreal forest using a 10-year time series of micrometeorological measurements and a Lagrangian stochastic model for particle transport. For a wide range of dispersal and life history types, we found positive relations between air temperature and LDD. This translates into a largely consistent positive effect of +3°C warming on predicted LDD frequencies and spread rates of plants. Relative increases in LDD frequency tend to be higher for heavy-seeded plants, whereas absolute increases in LDD and spread rates are higher for light-seeded plants for which wind is often an important dispersal vector. While these predicted increases are not sufficient to compensate forecasted range losses and environmental changes can alter plant spread in various ways, our results generally suggest that warming can promote wind-driven movements of plant genotypes and populations in boreal forests.
A New Formal Verification Approach for Hardware-dependent Embedded System Software

: This paper describes a method to generate a computational model for formal veriﬁcation of hardware-dependent software in embedded systems. The computational model of the combined HW / SW system is a program netlist (PN) consisting of instruction cells connected in a directed acyclic graph that compactly represents all execution paths of the software. The model can be easily integrated into SAT-based veriﬁcation environments such as those based on Bounded Model Checking (BMC). The proposed construction of the model allows for an e ﬃ cient reasoning of the SAT solver over entire execution paths. Program netlists are compositional. The paper presents how they can be combined to model interrupt-driven systems. We demonstrate the e ﬃ ciency of our approach by presenting experimental results from the formal veriﬁcation of an industrial LIN (Local Interconnect Network) bus node, implemented as a software driver on a 32-bit RISC machine.
LATERAL DOWNFLOWS IN SUNSPOT PENUMBRAL FILAMENTS AND THEIR TEMPORAL EVOLUTION

We study the temporal evolution of downflows observed at the lateral edges of penumbral filaments in a sunspot located very close to the disk center. Our analysis is based on a sequence of nearly diffraction-limited scans of the Fe i 617.3 nm line taken with the CRisp Imaging Spectro-Polarimeter instrument at the Swedish 1 m Solar Telescope. We compute Dopplergrams from the observed intensity profiles using line bisectors and filter the resulting velocity maps for subsonic oscillations. Lateral downflows appear everywhere in the center-side penumbra as small, weak patches of redshifts next to or along the edges of blueshifted flow channels. These patches have an intermittent life and undergo mergings and fragmentations quite frequently. The lateral downflows move together with the hosting filaments and react to their shape variations, very much resembling the evolution of granular convection in the quiet Sun. There is a good relation between brightness and velocity in the center-side penumbra, with downflows being darker than upflows on average, which is again reminiscent of quiet Sun convection. These results point to the existence of overturning convection in sunspot penumbrae, with elongated cells forming filaments where the flow is upward but very inclined, and weak lateral downward flows. In general, the circular polarization profiles emerging from the lateral downflows do not show sign reversals, although sometimes we detect three-lobed profiles that are suggestive of opposite magnetic polarities in the pixel.
Lung function values from a longitudinal study of healthy children and adolescents

From a cohort of 543 healthy children and adolescents, subjects were studied annually to obtain longitudinal data so that precise predictive values for lung volumes and flows from ages 8 to 19 years could be obtained. Strict guidelines for subject selection and pulmonary function testing were used. These data are presented in a readily usable form as equations, graphs, and tables. Pediatr Pilmonol. 1989; 7:101–109.
Data‐driven methods towards learning the highly nonlinear inverse kinematics of tendon‐driven surgical manipulators

Accurate motion control of flexible surgical manipulators is crucial in tissue manipulation tasks. The tendon‐driven serpentine manipulator (TSM) is one of the most widely adopted flexible mechanisms in minimally invasive surgery because of its enhanced maneuverability in torturous environments. TSM, however, exhibits high nonlinearities and conventional analytical kinematics model is insufficient to achieve high accuracy.
Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning.
An integrated backstepping and sliding mode tracking control algorithm for unmanned underwater vehicles

In this paper, an integrated backstepping and sliding mode tracking control algorithm is developed for three-dimensional tracking control of unmanned underwater vehicles (UUV). The proposed control strategy combines with a kinematic controller and dynamic controller together. The kinematic controller integrates a bio-inspired model with the backstepping method while the dynamic controller uses robust sliding mode control. Unlike the traditional backstepping method suffering from the speed jump problem, the application of bio-inspired model can generate smooth and continuous velocity signal even in the large initial errors. Therefore, a smooth control signal can be obtained by dynamic controller without thruster control saturation. The effectiveness and efficiency of the proposed control strategy are demonstrated through simulations and comparison studies.
Program on Education Policy and Governance Working Papers Series School Turnarounds: Evidence from the 2009 Stimulus School Turnarounds: Evidence from the 2009 Stimulus

– The American Recovery and Reinvestment Act of 2009 (ARRA) targeted substantial School Improvement Grants (SIGs) to the nation's " persistently lowest achieving " public schools (i.e., up to $2 million per school annually over 3 years) but required schools accepting these awards to implement a federally prescribed school-reform model. Schools that met the " lowest-achieving " and " lack of progress " thresholds within their state had prioritized eligibility for these SIG-funded interventions. Using data from California, this study leverages these two discontinuous eligibility rules to identify the effects of SIG-funded whole-school reforms. The results based on these " fuzzy " regression-discontinuity designs indicate that there were significant improvements in the test-based performance of schools on the " lowest-achieving " margin but not among schools on the " lack of progress " margin. Complementary panel-based estimates suggest that these improvements were largely concentrated among schools adopting the federal " turnaround " model, which compels more dramatic staff turnover.