Miracle-dz/UniFAR-FTUs huggingface dataset:
Mating Systems and the Efficacy of Selection at the Molecular Level

Mating systems are thought to play a key role in molecular evolution through their effects on effective population size (Ne) and effective recombination rate. Because of reduced Ne, selection in self-fertilizing species is supposed to be less efficient, allowing fixation of weakly deleterious alleles or lowering adaptation, which may jeopardize their long-term evolution. Relaxed selection pressures in selfers should be detectable at the molecular level through the analyses of the ratio of nonsynonymous and synonymous divergence, Dn/Ds, or the ratio of nonsynonymous and synonymous polymorphism, πn/πs. On the other hand, selfing reveals recessive alleles to selection (homozygosity effect), which may counterbalance the reduction in Ne. Through population genetics models, this study investigates which process may prevail in natural populations and which conditions are necessary to detect evidence for relaxed selection signature at the molecular level in selfers. Under a wide range of plausible population and mutation parameters, relaxed selection against deleterious mutations should be detectable, but the differences between the two mating systems can be weak. At equilibrium, differences between outcrossers and selfers should be more pronounced using divergence measures (Dn/Ds ratio) than using polymorphism data (πn/πs ratio). The difference in adaptive substitution rates between outcrossers and selfers is much less predictable because it critically depends on the dominance levels of new advantageous mutations, which are poorly known. Different ways of testing these predictions are suggested, and implications of these results for the evolution of self-fertilizing species are also discussed.
Inhibition of Double-Stranded RNA-Dependent Protein Kinase PKR by Vaccinia Virus E3: Role of Complex Formation and the E3 N-Terminal Domain

ABSTRACT The human double-stranded RNA (dsRNA)-dependent protein kinase PKR inhibits protein synthesis by phosphorylating translation initiation factor 2α (eIF2α). Vaccinia virus E3Lencodes a dsRNA binding protein that inhibits PKR in virus-infected cells, presumably by sequestering dsRNA activators. Expression of PKR in Saccharomyces cerevisiae inhibits protein synthesis by phosphorylation of eIF2α, dependent on its two dsRNA binding motifs (DRBMs). We found that expression of E3 in yeast overcomes the lethal effect of PKR in a manner requiring key residues (Lys-167 and Arg-168) needed for dsRNA binding by E3 in vitro. Unexpectedly, the N-terminal half of E3, and residue Trp-66 in particular, also is required for anti-PKR function. Because the E3 N-terminal region does not contribute to dsRNA binding in vitro, it appears that sequestering dsRNA is not the sole function of E3 needed for inhibition of PKR. This conclusion was supported by the fact that E3 activity was antagonized, not augmented, by overexpressing the catalytically defective PKR-K296R protein containing functional DRBMs. Coimmunoprecipitation experiments showed that a majority of PKR in yeast extracts was in a complex with E3, whose formation was completely dependent on the dsRNA binding activity of E3 and enhanced by the N-terminal half of E3. In yeast two-hybrid assays and in vitro protein binding experiments, segments of E3 and PKR containing their respective DRBMs interacted in a manner requiring E3 residues Lys-167 and Arg-168. We also detected interactions between PKR and the N-terminal half of E3 in the yeast two-hybrid and λ repressor dimerization assays. In the latter case, the N-terminal half of E3 interacted with the kinase domain of PKR, dependent on E3 residue Trp-66. We propose that effective inhibition of PKR in yeast requires formation of an E3-PKR-dsRNA complex, in which the N-terminal half of E3 physically interacts with the protein kinase domain of PKR.
Towards the modeling of gaas based 850 nm VCSEL with oxide confinement

The paper presents the structure for an oxide confined vertical cavity surface- emitting laser (VCSEL) and the simulation results for its operation at 850 nm of the electromagnetic spectrum. In this kind of VCSEL, low-doped DBR layers as well as the barrier reduction layers within the DBRs are introduced, and it is found that the device finally yields good operational efficiency. Illustrations are made of a few features for the proposed device that govern it operational characteristics.
Phase Noise Reduction of a Quantum Dash Mode-Locked Laser in a Millimeter-Wave Coupled Opto-Electronic Oscillator

Quantum dash active region Fabry-Perot lasers emitting at 1570 nm without an absorbing section have been evaluated as an optical source for microwave signal generation. These devices self-pulsate at 39.9 GHz with a mode-beating spectral linewidth as narrow as 10 kHz. Integration of these devices into an Opto-Electronic Oscillator has been performed, demonstrating a phase noise reduction of more than 15 dB in the low-frequency range. Moreover, the measured phase noise spectrum is well explained by a rate equation model taking into account the feedback loop.
Homopolar 2-Pole Radial Permanent-Magnet Biased Magnetic Bearing With Low Rotating Loss

To satisfy the low loss requirement of magnetically suspended rotors, such as energy-storage flywheel, a novel radial permanent-magnet biased magnetic bearing (RPMB) with low rotating loss due to low flux fluctuation frequency in rotor core called homopolar 2-pole RPMB was proposed. A rotating loss separation method was also proposed, which was based on the Bertotti loss model, but without measurement of model's coefficients. In virtue of the flywheel equipped with the homopolar 2-pole RPMB and the 4-pole RPMB successively, two types of bearings' rotating loss could be separated from flywheel run-down loss. The experimental results showed that the classic loss accounts for the majority of each type bearing's rotating loss at 30 000 rpm, and the rotating loss of the homopolar 2-pole RPMB was slightly more than half of the homopolar 4-pole RPMB. It could be inferred that the effect on the loss reduction of homopolar 2-pole RPMB would be more significant, for high speed or large power applications.
The consistency between measurements of the femoral neck anteversion angle in DDH on three-dimensional CT and MRI

Background Three-dimensional computed tomography (3D CT) has been regarded by some investigators as the gold standard for measurements of the femoral neck anteversion angle (FNA) in developmental dysplasia of the hip (DDH), although a simple and reliable imaging method using a non-ionizing technique is needed. Purpose To determine the consistency between measurements of the FNA in DDH using 3D CT and magnetic resonance imaging (MRI) and to estimate the precision, reliability, and reproducibility of MRI for the measurement of the FNA and assess whether MRI could replace 3D CT. Material and Methods 3D CT and MRI were used to measure the FNA in 22 patients, including 18 girls and four boys, with a mean age of 3 years (age range, 1–7 years). All of the measurements were performed independently by two radiologists at different times. This exercise was repeated 2 weeks later by one of the radiologists. Results High consistency was found between the MRI and 3D CT measurements (intraclass correlation coefﬁcient [ICC] of 0.906, P < 0.05). The mean inter-observer and intra-observer agreements were high for MRI (ICC = 0.948 and 0.964, respectively, P < 0.05 for both) and for 3D CT (ICC = 0.942 and 0.966, respectively, P < 0.05 for both). Conclusion Compared with 3D CT, MRI provided a precise, reliable and reproducible method of measuring the FNA in DDH. MRI is recommended as an appropriate technique for measurement of the FNA in DDH, and this approach could replace 3D CT because it delivers no ionizing radiation and offers a better display of soft tissue pathological changes.
Ground and excited state density functional calculations with the Gaussian and augmented-plane-wave method

The calculation of the electronic structure of large systems by methods based on density functional theory has recently gained a central role in molecular simulations. However, the extensive study of quantities like excited states and related properties is still out of reach due to high computational costs. We present a new implementation of a hybrid method, the Gaussian and Augmented-Plane-Wave (GAPW) method, where the electronic density is partitioned in hard and soft contributions. The former are local terms naturally expanded in a Gaussian basis, whereas the soft contributions are expanded in plane-waves by using a low energy cutoff, without loss in accuracy, even for all-electron calculations. For the calculation of excitation energies a recently developed, time-dependent density functional response theory (TD-DFRT) technique is joined with the GAPW procedure. We demonstrate the accuracy of the method by comparison with standard quantum chemistry calculations for a set of small molecules. To highlight the performance and efficiency of GAPW we show calculations on systems with several thousands of basis functions.
Association of gait and balance disorders with age-related white matter changes

Objective: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers are evaluating the role of age-related white matter changes (ARWMC) as an independent determinant of the transition to disability in the elderly (65 to 84 years). We aimed at determining the influence of ARWMC on different objective measures of gait and balance. Methods: Six hundred thirty-nine nondisabled individuals were prospectively enrolled and are being followed-up for 3 years. Subjects are graded in three standardized categories of ARWMC (mild, moderate, and severe) according to central MRI reading. Quantitative tests of gait and balance include the Short Physical Performance Battery (SPPB; range: 0 [poor] to 12 [normal]), a timed 8-m walk, and a timed single leg stance test. Results: In cross-sectional analysis, deficiencies in gait and balance performance were correlated with the severity of ARWMC (SPPB: 10.2 ± 2.1 in the mild, 9.9 ± 2.0 in the moderate, 8.9 ± 2.6 in the severe group; p < 0.001). Walking speed correlated with the severity of ARWMC (1.24 ± 0.28 m/second in the mild, 1.18 ± 0.32 m/second in the moderate, and 1.09 ± 0.31 m/second in the severe group; p < 0.001). Balance was best in individuals with mild ARWMC (single leg stance time: 18.9 ± 10.8 seconds) compared with moderate and severe ARWMC (16.4 ± 10.8 and 13.6 ± 11.2 seconds) (p < 0.001). Physically inactive individuals had a higher risk of a pathologic SPPB score (moderate vs mild ARWMC: odds ratio 1.60, 95% CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to 2.80). Conclusions: Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk of limitations in mobility.
Development and implementation of intraoperative magnetic resonance imaging and its neurosurgical applications.

OBJECTIVE We describe the development and implementation of a new open configuration magnetic resonance imaging (MRI) system, with which neurosurgical procedures can be performed using image guidance. Our initial neurosurgical experience consists of 140 cases, including 63 stereotactic biopsies, 16 cyst drainages, 55 craniotomies, 3 thermal ablations, and 3 laminectomies. The surgical advantages derived from this new modality are presented. METHODS The 0.5-T intraoperative MRI system (SIGNA SP, Boston, MA), developed by General Electric Medical Systems in collaboration with the Brigham and Women's Hospital, has a vertical gap within its magnet, providing the physical space for surgery. Images are viewed on monitors located within this gap and can also be acquired in conjunction with optical tracking of surgical instruments, establishing accurate intraoperative correlations between instrument position and anatomic structures. RESULTS A wide range of standard neurosurgical procedures can be performed using intraoperative MRI. The images obtained are clear and provide accurate and immediate information to use in the planning and assessment of the progress of the surgery. CONCLUSION Intraoperative MRI allows lesions to be precisely localized and targeted, and the progress of a procedure can be immediately evaluated. The constantly updated images help to eliminate errors that can arise during frame-based and frameless stereotactic surgery when anatomic structures alter their position because of shifting or displacement of brain parenchyma but are correlated with images obtained preoperatively. Intraoperative MRI is particularly helpful in determining tumor margins, optimizing surgical approaches, achieving complete resection of intracerebral lesions, and monitoring potential intraoperative complications.
Bronchiectasis in children: Orphan disease or persistent problem? *

More than a decade ago, bronchiectasis unrelated to cystic fibrosis was termed an “orphan disease”, because it had become an uncommon clinical entity among children in the developed world. Bronchiectasis is more common among children in lower socioeconomic classes and in developing countries, presumably due to more frequent and recurrent respiratory infections, environmental airway irritants, poor immunization rates, and malnutrition. Reports from the Southern Pacific and from Alaska Native children reveal persistently high rates of childhood bronchiectasis. Better epidemiologic data throughout the world are needed to reassess the importance of this condition. The pathophysiology includes airway inflammation, mucus production, and regional airway obstruction, yet the reasons why some children develop bronchiectasis while other do not is unclear. The coexistence of asthma with bronchiectasis is associated with more severe disease, yet the impact of asthma therapy in children with both disorders has not been studied. Similarly, the pattern of antibiotic use for children with bronchiectasis varies by region with little data to justify one particular approach. It may be that public health measures aimed at improving living conditions for children and prevention of respiratory infections with antiviral vaccines will have more impact on childhood bronchiectasis than medical treatments in the future. Pediatr Pulmonol. 2002; 33:492–496. © 2002 Wiley‐Liss, Inc.
Plasma PAI-1 Levels in Obese Children – Effect of Weight Loss and Influence of PAI-1 Promoter 4G/5G Genotype

Summary An association between an increase in plasminogen activator inhibitor type 1 (PAI-1) and obesity, and also between elevated levels of PAI-1 and the presence of PAI-1 promoter 4G allele has been described in adults and can contribute to increased risk of cardiovascular disease. It has also been suggested that in adults a decrease in adiposity has beneficial effects on the haemostatic system. However, less information is available regarding adiposity and fibrinolysis in children. The aim of the present study is to evaluate the effect of weight loss and the influence of the PAI-1 promoter 4G/5G genotype on the fibrinolytic system and lipid parameters in obese children. The clinical groups included 102 obese children and 105 controls of similar age and sex distribution. A significant decrease in fibrinolytic activity due to a significant increase in PAI-1 antigen and activity levels was observed in the obese children in comparison with the control group. In obese children, no significant differences in PAI-1 levels between the PAI-1 4G/5G genotypes were obtained. A significant correlation was observed between PAI-1 antigenic and functional levels and body mass index (BMI), as well as between PAI-1 levels and both triglyceride and insulin levels. No correlation between PAI-1 levels and either cholesterol or glucose levels was observed. After a three-month period of treatment to reduce weight, an increase in fibrinolytic activity due to a decrease in PAI-1 levels was observed in the obese children who had reduced their BMI in comparison with the group of obese children who did not show a decrease in their BMI. No significant differences between the two groups with respect to the variations in tissue type plasminogen activator and fibrinogen levels were obtained after three months of intervention to reduce weight. A significant correlation was observed between variations in BMI and variations in PAI-1 levels, and a significant inverse correlation was also observed between previous PAI-1 levels and variation in PAI-1 levels. Therefore, the largest decrease in PAI-1 levels was observed in the obese children with the highest previous PAI-1 levels. In conclusion, a decrease in BMI in obese children shows a favourable effect on the fibrinolytic system due to a decrease in PAI-1 levels. However, no influence of 4G/5G genotype on PAI-1 levels was observed.
Diclofenac inhibits Kv 1 . 3 and Kir 2 . 1 expressions in human macrophages and affects the membrane potential and foam cell formation

Objective To investigate the effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in human macrophages and the membrane potential and foaming process of the macrophages. Methods The effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in cultured human monocyte-derived macrophages was investigated using real-time RT-PCR and Western blotting, and its effect on the membrane potential was analyzed with optical mapping of the membrane potential with voltage-sensitive dyes. The ratio of cholesterol ester (CE) in the macrophages following intake of oxidized low-density lipoprotein (OxLDL) was analyzed by an enzymatic fluorometric method. Results The expression of Kv1.3 and Kir2.1 channels in the macrophages were down-regulated by diclofenac (1.5 μmol/L and 15 μmol/L). Compared with those in the control group, Kv1.3 mRNA expression was reduced by over 80% and 90% (P<0.05), and Kir2.1 mRNA by over 20% and 30% (P>0.05), respectively; both their protein expression was reduced by over 10% and 60% with a dosedependent effect (P< 0.05). Diclofenac at the two doses dose-dependently reduced the surface fluorescence intensity of the macrophage, and the membrane potential was decreased by 28% and 54% , respectively (P<0.05). Incubation of the macrophages with 30 mg/L OxLDL for 60 h caused an obvious enlargement of the cell volume and deposition of numerous lipid granules in cytoplasm, resulting also in a CE/TC ratio over 50% (P<0.05). Diclofenac at 1.5 and 15 μmol/L both significantly decreased the CE/TC ratio to (23.624±3.34)% and (13.601±2.916)% (P<0.05), respectively, but this effect did not show a dose-response relationship (P>0.05). Conclusion Diclofenac can significant down-regulate the expression of Kv1.3 and Kir2.1 channels in human macrophages, lower their membrane potential and inhibit the process of foam cell formation.
Caution! DNA Crossing: Crystal Structures of Holliday Junctions*

A four-stranded DNA junction (Fig. 1a) was first proposed by Robin Holliday in 1964 as a structural intermediate in a mechanistic model to account for the means by which genetic information is exchanged in yeast (1). This mechanism for genetic exchange is now generally known as homologous recombination and the four-stranded intermediate as the Holliday junction. The general mechanism for recombination has undergone a number of revisions in detail, but the Holliday junction remains a key component in the process and in a growing number of analogous cellular mechanisms (reviewed in Refs. 2 and 3), including site-specific recombination (4), resolution of stalled replication forks (5, 6), DNA repair (7, 8), and phage integration (9). Consequently, the structural and dynamic properties of the Holliday junction have been the focus of intense study since the mid-1960s. As is often the case in science, a multitude of single crystal structures of Holliday junctions in various forms have been solved over a relatively short period of time but only after decades of disappointment. The first structures of junctions in complexes with recombination and DNA repair proteins were reported in 1997 and 1998 (10, 11), whereas junctions in RNA-DNA complexes (12, 13) and in DNA-only constructs (14, 15) emerged just as the twentieth century came to a close. In this review, we will focus on the structures of DNA-only junctions and their geometries, as defined by sequence and ion-dependent interactions.
Epilepsy and the natural history of Rett syndrome

Background: Rett syndrome (RTT) is a neurodevelopmental disorder primarily seen in females, most with a mutation in MECP2. Epilepsy has been reported in 50%–80%. Previous reports were based on small sample sizes or parent-completed questionnaires, or failed to consider the impact of specific MECP2 mutations. Methods: The Rare Disease Consortium Research Network for RTT is an NIH-funded project to characterize the clinical spectrum and natural history of RTT in advance of clinical trials. Evaluations include clinical status (classic vs atypical RTT), MECP2 mutations, clinical severity, and presence, frequency, and treatment of seizures. Results: Enrollment as of June 2008 is 602; 528 (88%) meet clinical criteria for classic RTT. Of these, 493 (93%) have MECP2 mutations. Age range was 8 months to 64 years. A total of 360 (60%) were reported to have seizures, including 315 (60%) classic and 45 (61%) atypical RTT. Physician assessment of the 602 indicated that 48% had seizures. There was no significant difference in seizure occurrence by race/ethnicity. A significant age impact for seizures was seen and seizures were infrequent before age 2 years. MECP2 mutations most frequently associated with epilepsy were T158M (74%) and R106W (78%), and less frequently R255X and R306C (both 49%). Individuals with seizures had greater overall clinical severity, and greater impairment of ambulation, hand use, and communication. Discussion: Seizures are common in Rett syndrome, have an age-related onset and occurrence, vary by mutation, and are associated with greater clinical severity. This information represents a key consideration for designing clinical trials.
Report on the workshop on analytical models

Analytical models are extremely useful and important tools for design engineering in many fields. They provide engineers with performance predictions for a specified design, and they also can assist in design improvements by identifying the sources of performance deficiencies.Currently analytical models are not commonly used for design engineering in HCI. However, university research has produced some promising results, and has led to exploratory development projects in several major corporations.
Diurnal Variation in the Responsiveness of the Hypothalamic‐Pituitary‐Adrenal Axis of the Male Rat to Noise Stress

Basal activity of the rat hypothalamic‐pituitary‐adrenal (HPA) axis is highly dynamic and displays both circadian and ultradian rhythmicity in corticosterone secretion. This study investigated the relationship between basal corticosterone pulsatility and the corticosterone response to noise during the early light phase when there are no endogenous corticosterone pulses and during the early dark phase when there are hourly pulses of corticosterone. An automated blood sampling system was used to collect blood in conscious male rats at 5‐min intervals before, during and after exposure to 10‐min periods of white noise (104 dB). Behavioural responses to noise were also monitored during these periods. During the early light phase (morning), there was a consistent corticosteroid response to noise with corticosterone concentrations rising rapidly and reaching peak values 10–15 min after the noise had ceased, following which circulating concentrations declined at a rate comparable to the hormones half‐life. A second noise stress, 80 min later, resulted in adaptation of the corticosterone response. During the early dark phase (evening), the corticosterone response to the noise was similar to that seen in the morning, although there was no adaptation to a second stimulus. During the evening, the inhibition of endogenous HPA activity after the sound was limited to 40 min following stress.