Miracle-dz/UniFAR-FTUs huggingface dataset:
A double-deletion mutation in the Pitx3 gene causes arrested lens development in aphakia mice.

The recessive aphakia (ak) mouse mutant is characterized by bilateral microphthalmia due to a failure of lens morphogenesis. We fine-mapped the ak locus to the interval between D19Umi1 and D19Mit9, developed new polymorphic markers, and mapped candidate genes by construction of a BAC contig. The Pitx3 gene, known to be expressed in lens primordia, shows zero recombination with the ak mutation on our intersubspecific intercross panel representing 1170 meioses. A recent report described a deletion in the intergenic region between Gbf1 and Pitx3 as the possible ak mutation. Our results differ in that we find not only the distant intergenic deletion, but also a much larger deletion directly in the Pitx3 gene, eliminating exon 1 and extending into intron 1 and the promoter region. Pitx3 transcript levels are severely reduced in ak/ak mice from E11.5 to newborn (5 +/- 1% of the wildtype levels at E13.5), while an involvement of the flanking Gbf1 and Cig30 genes in the aberrant lens development is highly unlikely based on expression analysis. We conclude that the ak mutation consists of two deletions, the larger of which removes part of Pitx3, indicating a crucial role of this gene in early lens development.
2-D FFT for Periodic Noise Removal on Strain Image & &

Abstract-Elastography is a non-invasive method in which stiffness of soft tissue is displayed as strain images to assist in detecting or classifying tumors. External tissue compression causes axial displacements which are subsequently computed and converted to strain. However, in this processing, periodic artifacts often corrupt the image quality severely. This paper presents a 2-D FFT removal algorithm for reducing such artifacts in ultrasonic strain imaging. Because the periodic pattern of the artifacts, we apply the 2-D FFT in the strain image to extract and remove the peaks which are corresponding to artifacts in the frequency domain. Computer simulations and in vitro testing demonstrate our proposed method performs quite well in removing strain image artifacts.
In vitro activity of midecamycin diacetate, a 16-membered macrolide, against Streptococcus pyogenes isolated in France, 1995-1999.

OBJECTIVE To compare the in vitro activity of midecamycin diacetate to that of five other macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin) and of clindamycin against 146 clinical isolates of Streptococcus pyogenes, with regard to three different phenotypes of erythromycin resistance. METHODS Susceptibility pattern and resistance phenotype were determined by disk diffusion method and double disk test. Minimal inhibitory concentrations of antibiotics were obtained by the agar dilution method and evaluated according to the recommendations of the 'Comité de l'Antibiogramme de la Société Française de Microbiologie' (CA-SFM). The major determinants of erythromycin resistance in S. pyogenes (ermB, ermTR and mefA genes) were investigated by specific amplification protocols. RESULTS Most of the isolates of S. pyogenes collected during 1995-99 were susceptible to midecamycin (93.8%), erythromycin (90.4%), clarithromycin (93.2%), roxithromycin (91.8%), azithromycin (88.4%), josamycin (94.5%), and clindamycin (94.5%). According to the CA-SFM criteria, 132 of the 146 isolates studied were susceptible to erythromycin (MICs < or = 1 mg/L), four were intermediate (MICs 2-4 mg/L), and 10 were resistant (MICs > 4 mg/L). Only nine isolates were midecamycin resistant (MICs > 4 mg/L), and the others were susceptible. The increased activity of midecamycin (MIC90 < or = 0.06 mg/L), as compared to erythromycin (MIC90 = 0.5 mg/L) and to other 14- or 15-membered macrolides, was related to the absence of the ermB determinant in seven isolates which displayed an efflux phenotype (five isolates) or an inducible resistance phenotype due to an ermTR determinant (two isolates). CONCLUSION Midecamycin diacetate is active against most S. pyogenes strains isolated in France and may represent an attractive alternative to the treatment of streptococcal infections due to resistant isolates with efflux of erythromycin.
Impact of Subclinical Hypothyroidism on Cardiometabolic Biomarkers in Women

Context: Whether subclinical hypothyroidism (SCH) is associated with cardiometabolic abnormalities is uncertain. Objective: To examine diverse cardiometabolic biomarkers across euthyroid, SCH, and overt hypothyroidism (HT) in women free of cardiovascular disease. Design: Cross-sectional adjusted associations for lipids, lipoprotein subclasses, lipoprotein insulin resistance score, inflammatory, coagulation, and glycemic biomarkers by analysis of covariance for thyroid categories or thyroid stimulating hormone (TSH) quintiles on a Women’s Health Study subcohort. Setting: Outpatient. Patients or Other Participants: Randomly sampled 3914 middle-aged and older women for thyroid function analysis (TSH, free T4), of whom 3321 were not on lipid-lowering therapy. Intervention: None. Main Outcome Measure: Associations of SCH and HT with cardiometabolic markers. Results: Going from euthyroid to HT, the lipoprotein subclass profiles were indicative of insulin resistance (respective values and P for trend): larger very-low-density lipoprotein size (nm) (51.5 [95% confidence interval (CI), 51.2, 51.8] to 52.9 [51.8, 54.1], P = 0.001); higher low-density lipoprotein (LDL) particle concentration (nmol/L) [1283 (95% CI, 1267, 1299) to 1358 (1298, 1418), P = 0.004], and smaller LDL size. There was worsening lipoprotein insulin resistance score from euthyroid (49.2; 95% CI, 48.3, 50.2) to SCH (52.1; 95% CI, 50.1, 54.0) and HT (52.1; 95% CI, 48.6, 55.6); P for trend of 0.008. Of the other biomarkers, SCH and HT were associated with higher high-sensitivity C-reactive protein and hemoglobin A1c. For increasing TSH quintiles, results were overall similar. Conclusions: In apparently healthy women, SCH cardiometabolic profiles indicated worsening insulin resistance and higher cardiovascular disease risk markers compared with euthyroid individuals, despite similar LDL and total cholesterol. These findings suggest that cardiometabolic risk may increase early in the progression toward SCH and overt HT.
Fixed-value impulse noise suppression for images using PDE based Adaptive Two-Stage Median Filter

This paper presents a newly devised noise filter namely, Adaptive Two-Stage Median Filter (ATSM) to denoise the images corrupted by fixed-value impulse noise. The performance of the proposed filter is proved to be better in terms of Peak Signal-to-Noise Ratio and human visual perception. This filter is effectual in denoising the highly corrupted image with the noise probability of 90%.
Transferability of Skills across Sectors and Heterogeneous Displacement Costs

We use rich German administrative data to estimate new measures of skill transferability between manufacturing and other sectors. These measures capture the value of workers' human capital when applied in different sectors and are directly related to workers' displacement costs. We estimate these transferability measures using a selection correction model, which addresses workers' endogenous mobility, and a novel selection instrument based on the social network of workers. Our results indicate substantial heterogeneity in how workers can transfer their skills when they move across sectors, which implies heterogeneous displacement costs that depend on the sector to which workers reallocate.
Visual Function and Subjective Quality of Life in Chinese Cataract Patients after Implantation with Aspheric Intraocular Lenses

Purpose. To evaluate and compare the objective and subjective visual function after implantation of 2 aspheric intraocular lenses (IOLs) in Chinese cataract patients. Methods. Forty-one eyes of 28 patients with cataract were randomly assigned to receive either the MC X11 ASP IOL or the AcrySof IQ IOL. Three months postoperatively, best-corrected visual acuity (BCVA), contrast sensitivity, wavefront aberrations, and subjective visual quality were measured. The degree of posterior capsule opacification (PCO) was recorded at last follow-up. Results. Postoperative mean monocular BCVA was 0.05±0.13 logMAR in the MC X11 group and 0.05±0.08 logMAR in the IQ group. There was no significant difference in visual acuity, contrast sensitivity, subjective visual quality, and degree of PCO between the 2 groups. For a 6-mm pupil diameter, the mean spherical aberration (Z40) was 0.075±0.076 μm in the MC X11 group and 0.056±0.111 μm in the IQ group. However, 45.5% and 57.9% of the eyes in the MC X11 and IQ groups had values >0.10 μm, respectively. The mean RMS values of the high-order aberrations were similar between the 2 groups except the higher fifth- and sixth-order aberrations, which were significantly higher in the MC X11 group. Conclusions. Both IOLs provided similar and good visual outcomes. However, the data suggest that the amount of negative spherical aberration generated by current available aspheric IOLs might not be optimal for Chinese eyes.
Escargot and Scratch regulate neural commitment by antagonizing Notch activity in Drosophila sensory organs

During Notch (N)-mediated binary cell fate decisions, cells adopt two different fates according to the levels of N pathway activation: an Noff-dependent or an Non-dependent fate. How cells maintain these N activity levels over time remains largely unknown. We address this question in the cell lineage that gives rise to the Drosophila mechanosensory organs. In this lineage a primary precursor cell undergoes a stereotyped sequence of oriented asymmetric cell divisions and transits through two neural precursor states before acquiring a neuron identity. Using a combination of genetic and cell biology strategies, we show that Escargot and Scratch, two transcription factors belonging to the Snail superfamily, maintain Noff neural commitment by directly blocking the transcription of N target genes. We propose that Snail factors act by displacing proneural transcription activators from DNA binding sites. As such, Snail factors maintain the Noff state in neural precursor cells by buffering any ectopic variation in the level of N activity. Since Escargot and Scratch orthologs are present in other precursor cells, our findings are fundamental for understanding precursor cell fate acquisition in other systems. Summary: Two Snail family transcriptional regulators - Escargot and Scratch - redundantly repress Notch target gene transcription and, as such, maintain a silenced Notch pathway in neural precursor cells.
Learning through Hand- or Typewriting Influences Visual Recognition of New Graphic Shapes: Behavioral and Functional Imaging Evidence

Fast and accurate visual recognition of single characters is crucial for efficient reading. We explored the possible contribution of writing memory to character recognition processes. We evaluated the ability of adults to discriminate new characters from their mirror images after being taught how to produce the characters either by traditional pen-and-paper writing or with a computer keyboard. After training, we found stronger and longer lasting (several weeks) facilitation in recognizing the orientation of characters that had been written by hand compared to those typed. Functional magnetic resonance imaging recordings indicated that the response mode during learning is associated with distinct pathways during recognition of graphic shapes. Greater activity related to handwriting learning and normal letter identification was observed in several brain regions known to be involved in the execution, imagery, and observation of actions, in particular, the left Broca's area and bilateral inferior parietal lobules. Taken together, these results provide strong arguments in favor of the view that the specific movements memorized when learning how to write participate in the visual recognition of graphic shapes and letters.
Vascular endothelial growth factor expression coincides with coronary vasculogenesis and angiogenesis

Vascular endothelial growth factor (VEGF) plays an important role in early embryonic vasculogenesis. To establish its temporal expression and localization in the heart during development, we studied rat hearts from the first embryonic day (E) of myocardial vascular tube formation through the early postnatal period. Ventricular VEGF immunoreactivity was noted in the epicardium and the thin underlying myocardium in E10 ventricles. During the earliest stages of vascularization (E13–E16) immunoreactivity was highest in the compact myocardium nearest the epicardium, and subsequently (E18 and thereafter) became more evenly distributed transmurally. By birth (E22) immunoreactivity was most intense around microvessels. Similarly, VEGF mRNA localization, demonstrated by in situ hybridization, was initially highest near the epicardium and then became more evenly distributed transmurally by late gestation. Within the interventricular septum, the highest expression occurred in the middle of the wall where it correlated with the greatest vascularization. Northern blot analysis showed that from E12 through the first 10 days of postnatal life, VEGF was two to three times higher than in the adult. Western blot analysis showed that VEGF tended to be higher in the atria than the ventricles, and negligible in the outflow tract. Our data indicate that VEGF localization and expression 1) correspond to the pattern of vascularization in the embryonic/fetal heart, and 2) remain high during the early postnatal period when capillary proliferation is high. Because VEGF is stimulated by hypoxia, its preferential mRNA expression near the epicardium, that is, farthest from the ventricular lumen and the O2 source, fits with the hypothesis that a hypoxic gradient is a driving force in the transmural vascularization process. Dev Dyn 1999;215:54–61. © 1999 Wiley‐Liss, Inc.
Detection and quantification of rare mutations with massively parallel sequencing

The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Although massively parallel sequencing instruments are in principle well suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. The keys to this approach, called the Safe-Sequencing System (“Safe-SeqS”), are (i) assignment of a unique identifier (UID) to each template molecule, (ii) amplification of each uniquely tagged template molecule to create UID families, and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are considered mutant (“supermutants”) only if ≥95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro, and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.
Pharmacodynamic comparison of pantoprazole enantiomers: inhibition of acid‐related lesions and acid secretion in rats and guinea‐pigs

Pantoprazole is an irreversible proton pump inhibitor that is administered as a racemic mixture clinically. The effects of pantoprazole sodium (PAN·Na) enantiomers on acid‐related lesions were compared using models of pylorus ligation induced ulcer, histamine induced ulcer and reflux oesophagitis in rats and guinea‐pigs. Compared with (+)‐PAN·Na and (±)‐PAN·Na, (‐)‐PAN·Na showed much stronger inhibitory effects on pylorus ligation induced and histamine induced ulcers, but similar effects on reflux oesophagitis. The doses of (‐)‐PAN·Na, (+)‐PAN·Na and (±)‐PAN·Na required for 50% inhibition (ID50) of acid‐related lesions were 1.28, 5.03 and 3.40 mg kg−1 against pylorus ligation induced ulcer, 1.20, 4.28 and 3.15 mg kg−1 against histamine induced ulcer, and 2.92, 3.56 and 3.70 mg kg−1 against reflux oesophagitis, respectively. The inhibitory effects of PAN·Na enantiomers on basal gastric acid output were compared in rats with acute fistula. In contrast to inhibitory rates of 89.3% and 83.6% on gastric acid output by (‐)‐PAN·Na and (±)‐PAN·Na at 1.5 mg kg−1, (+)‐PAN·Na had an inhibitory rate of only 24.7% at the same dose. The above results indicate that (‐)‐PAN·Na is more potent than (+)‐PAN·Na at inhibiting acid‐related lesions owing to its stronger inhibition of acid secretion.
The importance of coagulation factors binding to adenovirus: historical perspectives and implications for gene delivery

Introduction: The interaction of human adenovirus (HAdV) serotype 5 (HAdV-5) with the blood coagulation factor X (FX) results in a high liver transduction after AdV intravascular administration, causing toxicity and limiting AdV delivery to the target tissue. However, FX also protects adenoviral vectors from neutralization by the complement system and natural antibodies, potentially benefiting adenoviral gene delivery, as neutralization results in the reduction of HAdV-5 binding to host cells. Areas covered: This review gives an overview on the use of adenoviruses as gene transfer vehicles and their impact in gene therapy. The structure of coagulation factors and their interactions with HAdV are described, highlighting their influence on the AdV biodistribution profile. The implications of this interaction in immunity and its potential influence on the use of adenoviral vectors in gene therapy applications are discussed. Expert opinion: The protective role of FX brings under discussion how beneficial abolishment of FX binding would be for HAdV-5 liver detargeting. The dispensability of FX for liver transduction in immunocompromised mice suggests the involvement of other blood factors or receptors in enhancing HAdV-5 liver transduction. Better understanding of the interactions that take place in the bloodstream is essential to generate safe and efficient adenoviral vectors.
Work stress in the etiology of coronary heart disease--a meta-analysis.

OBJECTIVES This study focused on estimating the relative risk of coronary heart disease (CHD) in association with work stress, as indicated by the job-strain model, the effort-reward imbalance model, and the organizational injustice model. METHODS A systematic review and meta-analysis of prospective cohort studies were carried out. Studies were eligible if they had published a quantitative estimate of the association between work stress and incident CHD or cardiovascular mortality by January 2006. RESULTS Fourteen prospective cohort studies were identified. For a total of 83 014 employees, the age- and gender-adjusted relative ratio of CHD for high versus low job strain was 1.43 [95% confidence interval (95% CI) 1.15-1.84], but the ratio decreased to 1.16 (95% CI 0.94-1.43) after adjustment for risk factors and potential mediators. The age- and gender-adjusted risk ratio for a combination of high efforts and low rewards was 1.58 (95% CI 0.84-2.97) for 11 528 employees, and no reduction in the risk ratio was seen after further adjustments. For organizational injustice, the age- and gender-adjusted, and multiple-adjusted relative risks were 1.62 (95% CI 1.24-2.13) and 1.47 (95% CI 1.12-1.95), respectively, for a population of 7246 men and women. There was little standardization in the assessment of work stress within all three stress models, and significant heterogeneity in the effects of stress was observed between studies. Few studies were available for female samples. CONCLUSIONS Observational data suggest an average 50% excess risk for CHD among employees with work stress. Further research is needed to confirm that a reduction in work stress will lead to a reduction in CHD risk.
Hypoxia and reoxygenation of brain microvascular smooth muscle cells in vitro: cellular responses and expression of cerebral amyloid angiopathy‐associated proteins

Hypoxia is known to cause complex cascades of physiological, biochemical, and morphological changes in the brain. Cerebral microvascular smooth muscle cell (MV‐SMC) damage may occur following hypoxic conditions and lead to SMC dysfunction. However, little is known about the exact cellular and molecular responses of these cells to hypoxia. To partly address these questions, MV‐SMC were isolated from human brain, cultured and placed in conditions of ambient hypoxia (H) and hypoxia followed by reoxygenation (H/R). Cell morphology, proliferation, and the expression of amyloid precursor protein (APP) and cystatin C peptide were investigated and compared (after induction of hypoxia) between cerebral MV‐ and human aortic SMC. Our results show that MV‐SMC proliferation was inhibited after 48 h of hypoxia and H/R, whereas aortic SMC proliferation was stimulated after 48 h of hypoxia and H/R. Hypoxia and H/R induced an increase of intracellular APP and cystatin C expression in both types of SMC, though the effect of H and H/R on APP upregulation was quantitatively more robust in MV‐SMC than aortic SMC. Patterns of hypoxia‐induced APP upregulation in SMC differed significantly from those found in cultured neuronal cells (PC12, NT2). These results suggest that hypoxia and H/R‐induced APP and cystatin C upregulation appear to occur independently of the inhibition of cerebral MV‐SMC proliferation. Overexpression of APP and cystatin C in response to hypoxia may thus represent an initiating event in the pathogenesis of amyloid angiopathy, or mediate progression of this microvascular lesion.
Korea's Challenges Ahead-Lessons from Japan's Experience

This paper draws out the parallels between Korea and Japan in terms of demographics, potential growth, balance sheets, asset prices and inflation. Korea’s demographic trends seem to track Japan’s with a lag of about 20 years. Low productivity in the service sector and labor market duality are common to both countries and need to be addressed with structural reforms. While Korea’s corporate balance sheets are stronger than Japan’s in the early 1990s, Korea needs to progress with the restructuring of nonviable firms to avoid the adverse consequences of delayed balance-sheet repair that Japan experienced. Given its strong fiscal balance sheet position, Korea can afford using fiscal policy actively to incentivize corporate restructuring and structural reforms and cushion their possible short-term adverse impact. Korea can prevent bubbles in asset prices that were at the origin of Japan’s initial crisis with the continued use of macroprudential policies. Although Korea does not appear to be headed toward deflation, new econometric analysis presented in the paper suggests that aging will exert a downward drag on its inflation going forward.