Miracle-dz/UniFAR-FTUs huggingface dataset:
Amino acid composition of α1/α2 domains and cytoplasmic tail of MHC class I molecules determine their susceptibility to human cytomegalovirus US11‐mediated down‐regulation

During co‐evolution with its host, human cytomegalovirus has acquired multiple defense mechanisms to escape from immune recognition. In this study, we focused on US11, which binds to MHC class I heavy chains and mediates their dislocation to the cytosol and subsequent degradation by proteasomes. To examine which domains of class I heavy chains are involved in this process, we constructedchimeric HLA molecules of US11‐sensitive and ‐insensitive class I molecules (HLA‐A2 and HLA‐G, respectively). Pulse‐chase experiments were performed to evaluate protein stability and interactions between class I heavy chains and US11. Flow cytometry was employed to assess the effect of US11 on surface expression of the different chimeras. Our results indicate that the α1 and α2 domains of HLA molecules are important for the affinity of US11 association. However, the degradation efficiency seems to rely mostly on cytosolic tail residues. We found that the nonclassical HLA‐G molecule is insensitive to US11‐mediated degradation solely because it lacks essential tail residues. A deletion of the last two tail residues in full‐length MHC class I molecules already caused a severe reduction in degradation efficiency. Altogether, our data provide new insights into the mechanism by which US11 down‐regulates MHC class I molecules.
Investigations on the Postnatal Development of the Macroscopic Proportions and the Topographic Anatomy of the Feline Spinal Cord

The aim of this work was to investigate the postnatal development of the feline spinal cord. Our study showed that the main period of growth leading to the cervical and lumbar enlargements begins after birth and is completed at the age of 5–6 months. Comparing the relationship between the length of the spinal cord and the vertebral column, we found that in contrast to the adult cat, in the newborn cat, length, area and volume of segments show similar values along the spinal cord. This also applied to the length of the vertebrae.
Identification of Src, Fyn, Lyn, PI3K and Abl SH3 domain ligands using phage display libraries.

Many proteins involved in intracellular signal transduction contain a small, 50‐60 amino acid domain, termed the Src homology 3 (SH3) domain. This domain appears to mediate critical protein‐protein interactions that are involved in responses to extracellular signals. Previous studies have shown that the SH3 domains from several proteins recognize short, contiguous amino acid sequences that are rich in proline residues. While all SH3 recognition sequences identified to date share a conserved P‐X‐X‐P motif, the sequence recognition specificity of individual SH3 domains is poorly understood. We have employed a novel modification of phage display involving biased libraries to identify peptide ligands of the Src, Fyn, Lyn, PI3K and Abl SH3 domains. With biased libraries, we probed SH3 recognition over a 12 amino acid window. The Src SH3 domain prefers the sequence XXXRPLPPLPXP, Fyn prefers XXXRPLPP(I/L)PXX, Lyn prefers RXXRPLPPLPXP, PI3K prefers RXXRPLPPLPP while the Abl SH3 domain selects phage containing the sequence PPPYPPPP(I/V)PXX. We have also analysed the binding properties of Abl and Src SH3 ligands. We find that although the phage‐displayed Abl and Src SH3 ligands are proline rich, they are distinct. In surface plasmon resonance binding assays, these SH3 domains displayed highly selective binding to their cognate ligands when the sequences were displayed on the surface of the phage or as synthetic peptides. The selection of these high affinity SH3 peptide ligands provides valuable information on the recognition motifs of SH3 domains, serve as new tools to interfere with the cellular functions of SH3 domain‐mediated processes and form the basis for the design of SH3‐specific inhibitors of disease pathways.
Computerized quantitative analysis of left ventricular wall motion by two-dimensional echocardiography.

Quantitative detection of left ventricular segmental wall motion abnormalities by any modality depends on the reference system used because of the dynamic geometry of contraction and cardiac motion within the thorax. To assess the feasibility and accuracy of quantitative analysis of left ventricular wall motion by two-dimensional echocardiography, we studied 61 subjects with the use of 44 different reference methods in each of three echocardiographic views: the parasternal short-axis view at the levels of the mitral valve and of the papillary muscles and an apical four-chamber view. The three major groups of reference systems used were those with a fixed external reference, a floating reference correcting for translation, and systems correcting for both translation and rotation. In the first part of this study the end-diastolic and end-systolic outlines of 20 normal subjects were stored in a computer and composite data of these 20 subjects were plotted to obtain a 95% confidence interval for measured normal fractional change for each reference method. In the second part of the project an additional prospective group of 10 normal subjects and a group of 31 "abnormal" patients had their left ventricular wall motion analyzed by similar methods and the results were compared with all the confidence intervals. One reference method was selected for each two-dimensional echocardiographic view based on the highest sensitivity and specificity found by statistical analysis; a floating-reference system including translation was found to be optimal for the apical four-chamber and parasternal short-axis views at the level of the mitral valve and a fixed external reference system was optimal for the short-axis view at the papillary level. The percent fractional shortening of radial dimensions (radial methods) and the percent fractional change in area measurements (area methods) during the cardiac cycle were also calculated at 5, 10, 20, 30 and 45 degree intervals around the outline perimeter for each subject according to each of the 44 different methods. Area methods yielded the same specificity and sensitivity as radial dimension analysis methods at 5 to 45 degree intervals. Ten normal subjects underwent repeat echocardiography within 2 days of their first study to examine day-to-day variation. Average change in mean contraction from day to day was 7% to 9% for radial methods and 9% to 13% for area methods. In conclusion, we present a computerized system for unbiased selection of optimal methods of analysis of left ventricular wall motion by two-dimensional echocardiography. (ABSTRACT TRUNCATED AT 400 WORDS)
Comparison of different fixed antihypertensive combination drugs: a double‐blind, placebo‐controlled parallel group study

Objective To compare the effects of fixed-dose preparations containing 180 mg sustained-release verapamil and 2 mg trandolapril, 100/25 mg atenolol/chlorthalidone, 20/12.5 mg lisinopril/ hydrochlorothiazide and placebo in patients with essential hypertension. Design A 4-week placebo run-in period followed by a double-blind, placebo-controlled parallel group study lasting 8 weeks. Setting Office practices (21 centres). Patients Patients with essential hypertension (World Health Organization grades I or II); supine diastolic blood pressure 101–114 mmHg in week 4 of the run-in period; 215 patients were enrolled, of whom 205 were assigned randomly to double-blind therapy. Main outcome measures Reduction in supine and standing blood pressures. Results All three active treatments with a single daily dose were significantly more effective than was placebo in reducing the blood pressure of seated subjects (P = 0.0001). The reductions in sitting diastolic blood pressure (DBP) from baseline to the last visit with each active treatment were comparable: 13 mmHg [95% confidence interval (CI) 16–9] with sustained- release verapamil/trandolapril, 13 mmHg (16–9) with atenolol/chlorthalidone and 12 mmHg (15–8) with lisinopril/hydrochlorothiazide. Normalization of blood pressure (DBP < 90 mmHg) was observed in 48% of patients with sustained-release verapamil/trandolapril, in 46% with atenolol/chlorthalidone and in 40% with lisinopril/hydrochlorothiazide. Response rates (normalization of DBP or a reduction in DBP by > 10 mmHg) with each active treatment were 72% for sustained-release verapamil/trandolapril, 76% for atenolol/chlorthalidone and 69% for lisinopril/ hydrochlorothiazide. All three active treatments were tolerated well. Conclusion This study demonstrates that the low-dose combination sustained-release verapamil/trandolapril may be a suitable alternative for combinations containing a thiazide diuretic or a β-blocker for longer term management of hypertensive patients for whom combination therapy is indicated.
Clinical NECR in 18F-FDG PET scans: optimization of injected activity and variable acquisition time. Relationship with SNR

The injected activity and the acquisition time per bed position for 18F-FDG PET scans are usually optimized by using metrics obtained from phantom experiments. However, optimal activity and time duration can significantly vary from a phantom set-up and from patient to patient. An approach using a patient-specific noise equivalent count rate (NECR) modelling has been previously proposed for optimizing clinical scanning protocols. We propose using the clinical NECR on a large population as a function of the body mass index (BMI) for deriving the optimal injected activity and acquisition duration per bed position. The relationship between the NEC and the signal-to-noise ratio (SNR) was assessed both in a phantom and in a clinical setting. 491 consecutive patients were retrospectively evaluated and divided into 4 BMI subgroups. Two criteria were used to optimize the injected activity and the time per bed position was adjusted using the NECR value while keeping the total acquisition time constant. Finally, the relationship between NEC and SNR was investigated using an anthropomorphic phantom and a population of 507 other patients. While the first dose regimen suggested a unique injected activity (665 MBq) regardless of the BMI, the second dose regimen proposed a variable activity and a total acquisition time according to the BMI. The NEC improvement was around 35% as compared with the local current injection rule. Variable time per bed position was derived according to BMI and anatomical region. NEC and number of true events were found to be highly correlated with SNR for the phantom set-up and partially confirmed in the patient study for the BMI subgroup under 28 kg m−2 suggesting that for the scanner, the nonlinear reconstruction algorithm used in this study and BMI < 28 kg m−2, NEC, or the number of true events linearly correlated with SNR2.
Molecular determinant modulates thermal recovery kinetics and structural integrity of the bacterial BLUF photoreceptor

BLUF domains are flavin‐based photoreceptors which receive the blue light signal and are involved in the sensory transduction. We report a short BLUF photoreceptor (SnfB) in Stenotrophomonas sp. We have investigated photodynamic properties of C terminus truncated and several mutated SnfB proteins. Deletion of the extended C‐terminal residues alters the thermal recovery kinetics and also affects the integrity of the SnfB protein. Mutagenesis studies demonstrated that the conserved residues within and outside the flavin‐binding pocket also regulates the photocycle properties of the protein. These studies suggest that the C‐terminal residues outside the BLUF domain can tune the photodynamic properties of the BLUF protein.
The Long-Term Effects of Mindfulness-Based Cognitive Therapy as a Relapse Prevention Treatment for Major Depressive Disorder

Background: Mindfulness-based Cognitive Therapy (MBCT) is a relapse prevention treatment for major depressive disorder. Method: An observational clinical audit of 39 participants explored the long-term effects of MBCT using standardized measures of depression (BDI-II), rumination (RSS), and mindfulness (MAAS). Results: MBCT was associated with statistically significant reductions in depression from pre to post treatment. Gains were maintained over time (Group 1, 1–12 months, p = .002; Group 2, 13–24 months, p = .001; Group 3, 25–34 months, p = .04). Depression scores in Group 3 did begin to worsen, yet were still within the mild range of the BDI-II. Treatment variables such as attendance at “booster” sessions and ongoing mindfulness practice correlated with better depression outcomes (p = .003 and p = .03 respectively). There was a strong negative correlation between rumination and mindful attention (p < .001), consistent with a proposed mechanism of metacognition in the efficacy of MBCT. Conclusion: It is suggested that ongoing MBCT skills and practice may be important for relapse prevention over the longer term. Larger randomized studies of the mechanisms of MBCT with longer follow-up periods are recommended.
Expression of p27(KIP1) and cell proliferation in human retina and retinoblastoma.

BACKGROUND Retinoblastoma is a rare cancer of the eye, in which biallelic inactivation of the retinoblastoma gene is a hallmark. Although retinoblastoma protein (Rb) and p27(KIP1) block the cell cycle transition from G1- to S-phase, the interaction has not been confirmed in vivo. The aim of this study was to examine the correlation between the expression of p27(KIP1) and cell proliferation in human retina and retinoblastoma. MATERIALS AND METHODS Human retinoblastoma, surgically removed, was fixed by 4% paraformaldehyde. Then, paraffin-embedded tissue sections were examined using immunohistochemistry with anti-p27(KIP1) and anti-proliferating cell nuclear antigen (PCNA) antibodies. RESULTS Retinoblastoma tissue was adjacent to the normal retina in which tumor cells with homogeneous nuclei proliferated and it was impossible to identify the layer structure of the inner nuclear layer (INL) and the outer nuclear layer (ONL). In normal retina, PCNA-positive nuclei were not observed, whereas nuclear immunoreactivity for PCNA was detected in a variety of tumor cells. Many p27(KIP1)-positive nuclei were detected in INL and ONL, while p27(KIP1) immunoreactivity was not detected in retinoblastoma cells. CONCLUSION The correlation between disappearance of p27(KIP1) and induction of proliferation activity suggests that functional loss of Rb leads to down-regulation of p27(KIP1) and uncontrolled retinal cell proliferation.
Modal Analysis of Microstrip Antenna on Fiber Reinforced Anisotropic Substrates

In this communication, microstrip antenna on fiber reinforced anisotropic substrates has been considered in aerospace applications; however, the antenna's optical axis may not necessarily be colinear with any of the substrate's principal axes and that leads to a nondiagonal permittivity matrix (tensor). This work extends the studies of microstrip antenna on isotropic substrate and on uniaxial substrate to analyze antenna performance on fiber reinforced anisotropic substrates, where the permittivity matrix has five dielectric constants because of the substrate's fiber direction. The solution is based on modal analysis so that the wave immittance can be derived in a closed form. Analyses and experimental verification show that the antenna performance is strongly influenced not only by the permittivity along the principal axes but also by the fiber direction of the substrate.
Otopathogenic Pseudomonas aeruginosa strains as competent biofilm formers.

OBJECTIVE To determine whether Pseudomonas aeruginosa, a common cholesteatoma pathogen, known to form biofilms in other chronic infections, is capable of contributing to biofilm formation in cholesteatoma. DESIGN We tested 12 OPPA isolates for several aspects of biofilm formation, including adherence to human keratinocytes, expression of quorum-sensing genes, twitching motility, and production of extracellular matrix as determined by both crystal violet staining and carbazole reaction. RESULTS Ten OPPA strains demonstrated increased adherence (1.5- to 12-fold) to human keratinocytes relative to PAO1, a laboratory strain. Expression of las and rhl quorum-sensing products were detected in 11 OPPA strains. By crystal violet staining, we found biofilm formation in all OPPA strains equal to or greater than that found in PAO1 (2- to 18-fold). In addition, OPPA strains demonstrated mucoid characteristics, including down-regulation of twitching motility and increased alginate production. CONCLUSIONS Strains of OPPA isolated from cholesteatoma are strongly adherent to keratinocytes and capable of forming biofilm. In addition, OPPA strains have mucoid characteristics in vitro. When these bacteria assume a biofilm phenotype, they are highly resistant to antibiotics and host defenses. These data suggest that OPPA can contribute to biofilm formation in cholesteatoma, leading to the persistence of this infection.
Clearing amyloid through the blood–brain barrier

According to the amyloid hypothesis, accumulation of amyloid β‐peptide (Aβ) in the brain is the primary pathogenic event in Alzheimer's disease (AD). Recent evidence indicates that Aβ within the intravascular space is linked to Aβ deposited in the brain suggesting that transport of Aβ between the brain, blood and cerebrospinal fluid, and across the blood–brain barrier, regulates brain Aβ. Thus, understanding Aβ exchanges between brain and blood, and vice versa, and developing transport‐based systemic Aβ‐lowering strategies may provide new important insights into pathogenesis and therapeutic control of AD.
Functional MRI of brain activation induced by scanner acoustic noise

A method is introduced by which brain activation caused by the acoustic noise associated with echo planar imaging (EPI) is mapped. Two types of time series were compared. The first time series, considered the “task,” involved applying only EPI gradients for 20 s without the application of RF pulses, then, without pause, starting image collection. The second, considered the “control,” involved typical sequential image acquisition without the prior gradient pulses. Subtraction of the first 5 s of the two time series revealed signal enhancement mainly in the primary auditory cortex. The technique was validated using a motor cortex task that mimicked the hypothesized scanner noise induced activation.
Incompatibility for CD31 and human platelet antigens and acute graft‐versus‐host disease after bone marrow transplantation

Bone marrow transplantation (BMT) is often complicated by acute graft‐versus‐host disease (aGVHD). In patients transplanted with an HLA‐matched donor the occurrence of this complication is believed to be favoured by disparities at the minor histocompatibility antigens (mHA). However, few of these polymorphic molecules have been identified. We sought to determine whether donor/recipient incompatibility for HPA‐1, HPA‐2, HPA‐3, HPA‐5 or CD31 (codon 125) antigens represented a risk factor for aGVHD and genotyped these antigens in 70 bone marrow donors and their HLA‐identical recipients. All patients were children who received BMT for haematological malignancies at a single institution according to well‐defined therapy protocols. Statistical analysis showed that incompatibility for CD31 (codon 125) was a risk factor for grade II–IV aGVHD in the overall patient population, whereas HPA‐3 incompatibility predicted aGVHD occurrence in HLA‐A2 patients only. The magnitude of the aGVHD risk was directly related to the number of HPA/CD31 incompatibilities. No correlation was found between non‐identity for HPA/CD31 and aGVHD. Since incompatibility but not non‐identity for CD31 or HPA‐3 was a risk factor for aGVHD, we suggest that allelic variants of these molecules can serve as mHA in BMT recipients from HLA‐identical donors.
Lipoprotein(a) [Lp(a)] levels in middle-aged male runners and sedentary controls.

Serum Lipoprotein(a) [Lp(a)] concentration was compared between middle-aged well-trained Caucasian male endurance runners (N = 57), (mean age +/- SEM 47.8 +/- 0.7 yr) and age-, body mass-, and body mass index (BMI)-matched male nonathletic control subjects (N = 62), (mean age +/- SEM 48.7 +/- 0.8). The mean weekly training distance of the runners was (60.7 +/- 2.8 km.wk-1) at the time of testing. Median Lp(a) levels were not significantly different (P > 0.05) between the runners (15.0 mg.dl-1) and the control subjects (12.5 mg.dl-1). As expected, compared with control subjects, in runners levels of other lipoproteins and apoproteins were significantly more favorable for cardiovascular health (all P < 0.01). There was no significant relationship between Lp(a) and any other measured variable (lipid, anthropometric, or dietary) in the runners group. In the control group, the significant positive correlation between Lp(a) and LDL-C was no longer significant after correction for the estimated contribution of Lp(a) cholesterol to LDL-C. These cross-sectional data suggest that a lifestyle of moderate to intense exercise training does not exert a significant impact on the Lp(a) level.
Fundamental Duty Modulation of Dual-Active-Bridge Converter for Wide-Range Operation

This paper proposed a modulation scheme for the dual-active-bridge (DAB) converter to reduce rms current in wide-range operating conditions. The operating principle of the proposed fundamental duty modulation (FDM) is formulated based on the fundamental component analysis of the DAB converter. By modulating the PWM signals in the fundamental component domain, the optimal operation is implemented with a simple controller structure not requiring an operating mode classification, offline calculation, or current information. Operating characteristics including rms current level and ZVS characteristics are analyzed to compare loss breakdowns of the proposed scheme to those of recent related works. The proposed FDM achieves high efficiency under wide operation conditions due to reduced conduction level and wide ZVS range. Experimental results are obtained under various voltage gain and load conditions to confirm the operation of the proposed modulation scheme. A thorough experimental comparison with other sophisticated modulation schemes has verified the efficiency improvement of FDM.