Miracle-dz/UniFAR-FTUs huggingface dataset:
Strength of an interloop hydrogen bond determines the kinetic pathway in catalysis by Escherichia coli dihydrofolate reductase.

On the basis of X-ray crystallographic data, Sawaya and Kraut proposed that Met20 loop conformational changes modulate ligand specificity observed in the catalytic cycle for Escherichia coli dihydrofolate reductase (DHFR) [Sawaya, M. R. , and Kraut, J. (1997) Biochemistry 36, 586-603]. Interloop hydrogen bonds stabilize either a closed Met20 loop conformation observed in substrate complexes or an occluded Met20 loop conformation observed in product complexes, respectively. To test this model, we targeted a single hydrogen bond occurring exclusively in the closed Met20 loop conformation. Specifically, Asp122 in the betaF-betaG loop was independently substituted with asparagine, serine, and alanine-amino acids with decreasing abilities to hydrogen-bond. The kinetic analyses of the Asp122 mutants enabled the construction of kinetic schemes at pH 7.0 that demonstrate two striking features. First, a significant correlation exists between decreased binding of nicotinamide adenine dinucleotide phosphate, reduced (NADPH), and decreased hydride transfer rates resulting from these mutations. In other words, the interactions of Asp122 are along the reaction coordinate leading to the transition state. Second, substitutions for Asp122 alter the catalytic pathway preferred by wild-type DHFR under saturating conditions of substrate and cofactor. Overall, the steady-state rate contains contributions from the product off rates from the DHFR.5,6, 7,8-tetrahydrofolate (H4F) and DHFR.NADPH. H4F complexes and from the rate of hydride transfer. These mutational effects support the mechanistic model whereby interloop contacts regulate an equilibrium of Met20 loop conformations that, in turn, modulate ligand affinity and turnover.
Delayed Review in Repeated Relationships

Many theoretical results rely on delayed review of imperfect information for sustaining cooperative outcomes. Using two laboratory experiments, this paper shows that delayed review can hinder cooperation in practice through a mechanism not captured by standard theory. The experiments make use of two different but closely related environments: a repeated prisoner's dilemma game with imperfect monitoring and pre-programmed grim triggers (but flexibility about what action to choose before the trigger is set off), and a decision problem played against a computer with a known strategy. At odds with the theoretical predictions, subjects cooperate less in both experiments when information is delayed. The results can be rationalized by a simple stochastic choice model with a bias toward survival.
Relative age effects in fitness testing in a general school sample: how relative are they?

Abstract When children or adolescents are grouped by age or year of birth, older individuals tend to outperform younger ones. These phenomena are known as relative age effects (RAEs). RAEs may result directly from differences in maturation, but may also be associated with psychological, pedagogic or other factors. In this article, we attempt to quantify RAEs in a simple fitness task and to identify the mechanisms operating. Data come from a 5-year study of 2278 individuals that included repeated administrations of the 20 m shuttle run. We use mixed-effect modelling to characterise change over time and then examine residuals from these models for evidence of an effect for age relative to peers or for season of birth. Age alone appears to account for RAEs in our sample, with no effects for age relative to peers or month of birth. Age grouping produces large disparities for girls under 12, moderate ones for boys of all ages and negligible ones for girls between 12 and 15. RAEs for this task and population appear to arise from simple age differences. Similar methods may be useful in determining whether other explanations of RAEs are necessary in other contexts. Evaluation processes that take age into account have the potential to mitigate RAEs in general settings.
ITIL Adoption Model based on TAM

although Information technology infrastructure library (ITIL) is the most popular framework for IT service management all around the world, problems for organizations in the process of adoption would eliminate its benefits. In fact the ability of organization to adopt this framework is the basis for IT service improvement. Few studies have tried to find out success factor that influence ITIL adoption but no study was found investigating an adoption model for this framework. In this study, first seven success factors were identified through qualitative meta-Synthesis relying on previous studies; then, a research model based on the technology acceptance model (TAM) for representing the influence of these critical success factors on ITIL adoption is proposed. The success factor used are: (1) top management support, (2) communication and cooperation, (3) training and competence of involved stakeholder in ITIL project, (4) change management and organizational culture, (5) project management and governance, (6) ITIL process implementation and applied technology, (7) monitoring and evaluation.
Postpartum depression after mild and severe preeclampsia.

OBJECTIVE To describe the prevalence of postpartum depressive symptoms after preeclampsia, to assess the extent to which the prevalence of postpartum depressive symptoms differs after mild and severe preeclampsia, and to investigate which factors contribute to such differences. METHODS Women diagnosed with preeclampsia (n=161) completed the Edinburgh Postnatal Depression Scale (EPDS) at 6, 12, or 26 weeks postpartum. Multiple logistic regression analysis was used to investigate the association between severity of preeclampsia, contributing factors and postpartum depression (PPD) (1) at any time during the first 26 weeks postpartum and (2) accounting for longitudinal observations at three time points. RESULTS After mild preeclampsia, 23% reported postpartum depressive symptoms at any time up to 26 weeks postpartum compared to 44% after severe preeclampsia (unadjusted odds ratio [OR] 2.65, 95% confidence interval [CI] 1.16-6.05) for depression at any time up to 26 weeks postpartum (unadjusted OR 2.57, 95% CI, 1.14-5.76) while accounting for longitudinal observations. Admission to the neonatal intensive care unit (NICU) (adjusted OR 3.19, 95% CI 1.15-8.89) and perinatal death (adjusted OR 2.96, 95% CI 1.09-8.03) contributed to this difference. CONCLUSIONS It appears that not the severity of preeclampsia itself but rather the consequences of the severity of the disease (especially admission to the NICU and perinatal death) cause postpartum depressive symptoms. Obstetricians should be aware of the high risk of postpartum depressive symptoms after severe preeclampsia, particularly among women whose infant has been admitted to the NICU or has died.
Social contagion of correct and incorrect information in memory

The present study examines how discussion between individuals regarding a shared memory affects their subsequent individual memory reports. In three experiments pairs of participants recalled items from photographs of common household scenes, discussed their recall with each other, and then recalled the items again individually. Results showed that after the discussion. individuals recalled more correct items and more incorrect items, with very small non-significant increases, or no change, in recall accuracy. The information people were exposed to during the discussion was generally accurate, although not as accurate as individuals' initial recall. Individuals incorporated correct exposure items into their subsequent recall at a higher rate than incorrect exposure items. Participants who were initially more accurate became less accurate, and initially less-accurate participants became more accurate as a result of their discussion. Comparisons to no-discussion control groups suggest that the effects were not simply the product of repeated recall opportunities or self-cueing, but rather reflect the transmission of information between individuals.
Proteomic evaluation of cadmium toxicity on the midge Chironomus riparius Meigen larvae

Heavy‐metal pollution of aquatic ecosystems is a widespread phenomenon after industrial consumption. Whether aquatic organisms are adapted to the heavy‐metal pollutants or not, such environmental stress causes changes in physiological responses. In this study, the aquatic midge, Chironomus riparius Meigen, was used to find changes of expression of proteins in relation to cadmium exposure. Dose‐response relationships between cadmium concentrations and mortality of 3rd instar midge larvae were observed and the protein levels were compared using PD‐Quest after 2‐DE. Comparing the intensity of protein spots, 21 proteins decreased and 18 proteins increased in response to cadmium treatment. With increased proteins, three enzymes such as S‐adenosylmethionine decarboxylase, O‐methyltransferase, and aspartokinase were involved in the glutathione biosynthesis and a key enzyme regulating fatty acid biosynthesis, oleyl‐acyl carrier protein thioesterase was also identified. According to the functional classification of decreased levels of proteins, they were involved in energy production, protein fate, nucleotide biosynthesis, cell division, transport and binding, signal transduction, and fatty acid and phospholipid metabolism in the cell. In addition, phenol hydroxylase, thioesterase, zinc metalloprotease, and aspartate kinase were newly expressed after cadmium exposure at the concentration of the LC10 value. Therefore, these proteins seem to be potential biomarkers for cadmium exposure in the aquatic ecosystems.
Adenosine signaling, priapism and novel therapies.

INTRODUCTION Priapism is defined as abnormal prolonged penile erection lasting at least for 4 hours occurring without sexual interest. Forty percent of sickle cell disease (SCD) patients display priapism. The disorder is dangerous and urgent given its association with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. Current strategies to manage the disorder are poor due to lack of fundamental understanding of the molecular mechanisms of priapism. Adenosine is a signaling nucleoside that elicits many pathophysiological effects by engaging membrane receptors. Recent evidence shows that adenosine may play an important role in priapism via adenosine receptor. AIM To summarize the recent findings on the importance of adenosine signaling in the pathogenesis of priapism. MAIN OUTCOME MEASURES Evidence in the literature on the association between adenosine signaling and the development of priapism. METHODS This article reviews the literature that relates to the contributory role of adenosine signaling in priapism in multiple animal models and humans. RESULTS Excessive adenosine accumulation in the penis, coupled with increased A(2B)R signaling, contributes to priapism in two independent lines of mutant mice. One is adenosine deaminase (ADA)-deficient mice, the only animal displaying spontaneously prolonged penile erection, and the other is SCD transgenic mice, a well-accepted priapic animal model. Both polyethylene glycol-modified ADA (PEG-ADA) enzyme therapy and A(2B)R antagonists are capable of inhibiting potent corpus cavernosal vascular relaxation associated with priapic-like activity seen in both ADA-deficient mice and SCD transgenic mice, indicating that PEG-ADA enzyme therapy is likely to be a novel therapy for such a dangerous urological disorder. CONCLUSION Overall, the research reviewed here raises the intriguing possibility that elevated adenosine signaling contributes to priapism in general and that this signaling pathway represents a potentially important therapeutic target for the treatment of priapism.
Intracranial pressure response after pharmacologic treatment of intracranial hypertension

BACKGROUND The accepted treatment of increased intracranial pressure (ICP) in patients experiencing severe traumatic brain injury is multimodal and algorithmic, obscuring individual effects of treatment. Using continuous vital signs monitoring, we sought to measure treatment effect and ascertain the accuracy of manual data recording. METHODS Patients older than 17 years, admitted and requiring ICP monitoring between 2008 and 2010 at a high-volume urban trauma center, were retrospectively evaluated. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. ICP data were collected automatically at 6-second intervals and from manual charts. A statistical mixed model was applied to all data to account for multiple sampling. RESULTS A total of 117 patients met inclusion criteria; 450 treatments were administered when nursing records indicate an ICP greater than 20 mm Hg, while 968 treatments were given when ICP was greater than 20 mm Hg by automated data. Pharmacologic treatments identified include hypertonic saline (HTS), mannitol, barbiturates, and dose escalations of propofol or fentanyl infusions. Treatment with HTS resulted in the largest ICP decrease of the treatments examined, with a 1-hour ICP reduction of 8.8/9.9 mm Hg (for a small/large dose) according to manual data and a reduction of 3.0/2.4 mm Hg according to automated data. Propofol and fentanyl escalations resulted in smaller but significant ICP reductions. Mannitol (n = 8) resulted in statistically insignificant trends down in the first hour but rebounded by the second hour after administration. The average ICP in the hour before medication administration was higher for barbiturates (27 mm Hg) and mannitol (32 mm Hg) than for the other interventions (18–19 mm Hg). CONCLUSION ICP fell after administration of HTS, mannitol, or barbiturates and showed continued improvement after 2 hours. ICP fell initially after treatment with short-acting propofol and fentanyl but trended back up after 2 hours. Manually recorded data consistently overestimated treatment effectiveness. Automated data collection gives a more accurate assessment of patient status and responsiveness to treatment. LEVEL OF EVIDENCE Therapeutic study, level IV.
Preschoolers' use of desires to solve theory of mind problems in a pretense context.

K. Bartsch and H. M. Wellman (1995) have suggested that 3-year-old children's preference to construe behavior in terms of desire may interfere with their ability to reason according to belief in standard false belief tasks. Other researchers have suggested that young children fail typical measures of theory of mind because they have a reality bias (e.g., P. Mitchell, 1994). Study 1 demonstrates that even young children are able to correctly attribute a false belief to an agent when that belief is about the status of a pretense. Study 2 shows that children find it easier to attribute a false belief when the desires of the agent are eliminated. However, Study 3 suggests that a reality bias also influences children's ability to consider beliefs. Implications for recent accounts of theory of mind development are discussed.
Improved performance of 1.3-/spl mu/m In(Ga)As quantum-dot lasers by modifying the temperature profile of the GaAs spacer layers

We demonstrate greatly improved threshold current and modal gain performance of 1.3-/spl mu/m quantum-dot (QD) lasers by growing the GaAs spacer layers in two parts, where subtle modification of the spacer layer growth temperature profoundly influences the QDs. Measurements reveal significantly increased ground state (1.3 /spl mu/m) modal absorption by increasing the growth temperature of the second part of the spacer layer. Improved modal gain is achieved, enabling continuous-wave lasing from a 1-mm-long uncoated laser, even without p-doping. This approach provides a potentially viable route to superior edge-emitting lasers and GaAs-based 1.3-/spl mu/m vertical-cavity surface-emitting lasers.
Estimation and Pharmacodynamic Consequences of the Minimum Effective Anesthetic Volumes for Median and Ulnar Nerve Blocks: A Randomized, Double-Blind, Controlled Comparison Between Ultrasound and Nerve Stimulation Guidance

BACKGROUND:Nerve stimulation and ultrasound guidance are the most popular techniques for peripheral nerve blocks. However, the minimum effective anesthetic volume (MEAV) in selected nerves for both techniques and the consequences of decreasing the local anesthetic volume on the pharmacodynamic characteristics of nerve block remain unstudied. We designed a randomized, double-blind controlled comparison between neurostimulation and ultrasound guidance to estimate the MEAV of 1.5% mepivacaine and pharmacodynamics in median and ulnar nerve blocks. METHODS:Patients scheduled for carpal tunnel release were randomized to ultrasound guidance (UG) or neurostimulation (NS) groups. A step-up/step-down study model (Dixon method) was used to determine the MEAV with nonprobability sequential dosing based on the outcome of the previous patient. The starting dose of 1.5% mepivacaine was 13 and 11 mL for median and ulnar nerves at the humeral canal. Block success/failure resulted in a decrease/increase of 2 mL. A blinded physician assessed sensory blockade at 2-minute intervals for 20 minutes. Block onset time and duration were noted. RESULTS:The MEAV50 (SD) of the median nerve was lower in the UG group 2 (0.1) mL (95% confidence interval [CI] = [1, 96] to [2, 04]) than in the NS group 4 (3.8) mL (95% CI = [2, 4] to [5, 6]) (P = 0.017). There was no difference for the ulnar nerve between UG group 2 (0.1) mL (95% CI = [1, 96] to [2, 04]) and NS group 2.4 (0.6) mL (95% CI = [2, 1] to [2, 7]). The duration of sensory blockade was significantly correlated to local anesthetic volume, but onset time was not modified. CONCLUSION:Ultrasound guidance selectively provided a 50% reduction in the MEAV of mepivacaine 1.5% for median nerve sensory blockade in comparison with neurostimulation. Decreasing the local anesthetic volume can decrease sensory block duration but not onset time.
Molecular Cloning, Chromosomal Localization, Tissue Distribution, and Functional Expression of the Human Pancreatic Sodium Bicarbonate Cotransporter*

We report the cloning, sequence analysis, tissue distribution, functional expression, and chromosomal localization of the human pancreatic sodium bicarbonate cotransport protein (pancreatic NBC (pNBC)). The transporter was identified by searching the human expressed sequence tag data base. An I.M.A.G. E. clone W39298 was identified, and a polymerase chain reaction probe was generated to screen a human pancreas cDNA library. pNBC encodes a 1079-residue polypeptide that differs at the N terminus from the recently cloned human sodium bicarbonate cotransporter isolated from kidney (kNBC) (Burnham, C. E., Amlal, H., Wang, Z., Shull, G. E., and Soleimani, M. (1997) J. Biol. Chem. 272, 19111–19114). Northern blot analysis using a probe specific for the N terminus of pNBC revealed an ∼7.7-kilobase transcript expressed predominantly in pancreas, with less expression in kidney, brain, liver, prostate, colon, stomach, thyroid, and spinal chord. In contrast, a probe to the unique 5′ region of kNBC detected an ∼7.6-kilobase transcript only in the kidney. In situhybridization studies in pancreas revealed expression in the acini and ductal cells. The gene was mapped to chromosome 4q21 using fluorescentin situ hybridization. Expression of pNBC in Xenopus laevis oocytes induced sodium bicarbonate cotransport. These data demonstrate that pNBC encodes the sodium bicarbonate cotransporter in the mammalian pancreas. pNBC is also expressed at a lower level in several other organs, whereas kNBC is expressed uniquely in kidney.
Organizational Discourse and New Organization Development Practices

A new ensemble of organization development (OD) practices have emerged that are based more on constructionist, post modern and new sciences premises than the assumptions of the early founders. These include practices associated with appreciative inquiry, large group interventions, changing mindsets and consciousness, addressing diversity and multicultural realities, and advancing new and different models of change. We propose that the emerging field of organizational discourse offers sympathetic concepts and research that could add additional insights and theoretical rigour to the New OD. In particular, studies of organizational discourse based upon social constructionist and critical perspectives offer compelling ideas and practices associated with the establishment of change concepts, the role of power and context in relation to organizational change, and specific discursive interventions designed to foster organizational change.
Poverty and health behaviour: Comparing socioeconomic status and a combined poverty indicator as a determinant of health behaviour

Studies in the area of health economics and public health have shown that low socioeconomic status (SES) and poverty are related to lower levels of health. Attempts to explain these differences have often made reference to the observation that poor health behaviours cluster in low SES respectively poverty groups. However, relatively little attention has been paid to the defining concept of SES and its appropriate measurement. Therefore data from the German Socio-Economic Panel are used to analyse the relationship between two multidimensional measurements to describe a) poverty respectively b) a low SES and health behaviour, including dietary behaviour, weight status and health behaviour in general. This study shows that both multidimensional indicators allow identifying an inverse relationship between low SES respectively poverty and several types of health behaviour. However, comparing both indicators it is evident that individuals may be affected by poverty in different ways which has various effects on their health behaviour. Additionally, future research should focus not only on multidimensional poverty measurements but also on dynamic effects.
Behavioral Outcomes of Extremely Low Birth Weight Children at Age 8 Years

Objective: To describe the prevalence of behavioral problems and symptomatology suggestive of Autism and Asperger's disorders at age 8 years among extremely low birth weight (ELBW, <1 kg) children, born 1992 through 1995. Method: Parent reports of the behavior of 219 ELBW (mean birth weight, 810 g; gestational age 26 weeks) were compared with 176 normal birth weight children of similar maternal sociodemographic status, sex, and age. Behavior was assessed via the Child Symptom Inventory that includes both Symptom Severity Scores and scores meeting DSM-IV criteria for disorders. Results: ELBW compared with normal birth weight children had significantly higher mean Symptom Severity Scores for the inattentive, hyperactive, and combined types of attention-deficit hyperactivity disorder (all p < .001) as well as higher scores for Generalized Anxiety (p < .01) and Autistic (p < .001) and Asperger's (p < .01) disorders. When DSM-IV criteria were considered, ELBW children also had significantly higher rates of attention-deficit hyperactivity disorder of the inattentive (10% vs 3%, p < .01) and combined (5% vs 0.6%, p < .05) types. Conclusions: Attention-deficit hyperactivity disorder, mainly the inattentive type is prevalent among ELBW children. Our findings of an increase in symptoms pertaining to Autistic and Asperger's disorders at school age agree with recent reports of others during early childhood. Early identification and intervention for these problems might improve child functioning and ameliorate parent and child distress.