Miracle-dz/UniFAR-FTUs huggingface dataset:
Fgfr4 Is Required for Effective Muscle Regeneration in Vivo

Fgfr4 has been shown to be important for appropriate muscle development in chick limb buds; however, Fgfr4 null mice show no phenotype. Here, we show that staged induction of muscle regeneration in Fgfr4 null mice becomes highly abnormal at the time point when Fgfr4 is normally expressed. By 7 days of regeneration, differentiation of myotubes became poorly coordinated and delayed by both histology and embryonic myosin heavy chain staining. By 14 days much of the muscle was replaced by fat and calcifications. To begin to dissect the molecular pathways involving Fgfr4, we queried the promoter sequences for transcriptional factor binding sites and tested candidate regulators in a 27-time point regeneration series. The Fgfr4 promoter region contained a Tead protein binding site (M-CAT 5′-CATTCCT-3′), and Tead2 showed induction during regeneration commensurate with Fgfr4 regulation. Co-transfection of Tead2 and Fgfr4 promoter reporter constructs into C2C12 myotubes showed Tead2 to activate Fgfr4, and mutation of the M-CAT motif in the Fgfr4 promoter abolished these effects. Immunostaining for Tead2 showed timed expression in myotube nuclei consistent with the mRNA data. Query of the expression timing and genomic sequences of Tead2 suggested direct regulation by MyoD, and consistent with this, MyoD directly bound to two strong E-boxes in the first intron of Tead2 by chromatin immunoprecipitation assay. Moreover, co-transfection of MyoD and Tead2 intron reporter constructs into 10T1/2 cells activated reporter activity in a dose-dependent manner. This activation was greatly reduced when the two E-boxes were mutated. Our data suggest a novel MyoD-Tead2-Fgfr4 pathway important for effective muscle regeneration.
Cleavage Preferences of the Apoptotic Endonuclease DFF40 (Caspase-activated DNase or Nuclease) on Naked DNA and Chromatin Substrates*

Here we report the co-factor requirements for DNA fragmentation factor (DFF) endonuclease and characterize its cleavage sites on naked DNA and chromatin substrates. The endonuclease exhibits a pH optimum of 7.5, requires Mg2+, not Ca2+, and is inhibited by Zn2+. The enzyme generates blunt ends or ends with 1-base 5′-overhangs possessing 5′-phosphate and 3′-hydroxyl groups and is specific for double- and not single-stranded DNA or RNA. DFF endonuclease has a moderately greater sequence preference than micrococcal nuclease or DNase I, and the sites attacked possess a dyad axis of symmetry with respect to purine and pyrimidine content. Using HeLa cell nuclei or chromatin reconstituted on a 5 S rRNA gene tandem array, we prove that the enzyme attacks chromatin in the internucleosomal linker, generating oligonucleosomal DNA ladders sharper than those created by micrococcal nuclease. Histone H1, high mobility group-1, and topoisomerase II activate DFF endonuclease activity on naked DNA substrates but much less so on chromatin substrates. We conclude that DFF is a useful reagent for chromatin research.
The Molecular Basis of Antithrombin Deficiency in Belgian and Dutch Families

Summary The molecular basis of hereditary antithrombin (AT) deficiency has been investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these families had a quantitative or type I AT deficiency, with a history of major venous thromboembolic events in different affected members. In the other two families a qualitative or type II AT deficiency was occasionally diagnosed. DNA studies of the AT gene were performed, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and intronexon junction regions. Six novel point mutations were identified: four missense, one nonsense mutation and a single nucleotide deletion near the reactive site, causing a frameshift with premature translation termination. In two kindreds the underlying genetic defect was caused by a whole gene deletion, known as a rare cause of AT deficiency. In these cases, Southern blot and polymorphism analysis of different parts of the AT gene proved useful for diagnosis. In another kindred a partial gene deletion spanning 698 basepairs could precisely be determined to a part of intron 3B and exon 4. In two type I and in both type II AT deficient families a previously reported mutation was identified. In all cases, the affected individuals were heterozygous for the genetic defect.
Caffeine exposure alters adenosine system and neurochemical markers during retinal development

Evidence points to beneficial properties of caffeine in the adult central nervous system, but teratogenic effects have also been reported. Caffeine exerts most of its effects by antagonizing adenosine receptors, especially A1 and A2A subtypes. In this study, we evaluated the role of caffeine on the expression of components of the adenosinergic system in the developing avian retina and the impact of caffeine exposure upon specific markers for classical neurotransmitter systems. Caffeine exposure (5–30 mg/kg by in ovo injection) to 14‐day‐old chick embryos increased the expression of A1 receptors and concomitantly decreased A2A adenosine receptors expression after 48 h. Accordingly, caffeine (30 mg/kg) increased [3H]‐8‐cyclopentyl‐1,3‐dipropylxanthine (A1 antagonist) binding and reduced [3H]‐ZM241385 (A2A antagonist) binding. The caffeine time‐response curve demonstrated a reduction in A1 receptors 6 h after injection, but an increase after 18 and 24 h. In contrast, caffeine exposure increased the expression of A2A receptors from 18 and 24 h. Kinetic assays of [3H]‐S‐(4‐nitrobenzyl)‐6‐thioinosine binding to the equilibrative adenosine transporter ENT1 revealed an increase in Bmax with no changes in Kd, an effect accompanied by an increase in adenosine uptake. Immunohistochemical analysis showed a decrease in retinal content of tyrosine hydroxylase, calbindin and choline acetyltransferase, but not Brn3a, after 48 h of caffeine injection. Furthermore, retinas exposed to caffeine had increased levels of phosphorylated extracellular signal‐regulated kinase and cAMP‐response element binding protein. Overall, we show an in vivo regulation of the adenosine system, extracellular signal‐regulated kinase and cAMP‐response element binding protein function and protein expression of specific neurotransmitter systems by caffeine in the developing retina.
Occult Mucosal Injuries with Radiofrequency Ablation of the Palate

OBJECTIVE: To determine the true incidence of mucosal injury after radiofrequency ablation of the palate (RFAP) for snoring and mild obstructive sleep apnea, and to evaluate the consequences of this injury. STUDY DESIGN AND SETTING: A prospective, nonrandomized analysis of RFAP was undertaken at Stanford University Hospital. Endoscopic examinations of the nasal surface of the palate and of the posterior pharyngeal wall were performed to supplement the routine oral cavity examinations in the postoperative period. Visual analog scales of pain were completed by the patients. Twenty-three patients underwent a total of 54 RFAP procedures using the Somnus system at the recommended level of energy (600 J in the midline palate, and 300 J to each lateral palate). RESULTS: Fourteen of the 23 first stage procedures were associated with a total of 16 mucosal injuries representing an incidence of 60.9%. Mucosal injury at the 1st stage prompted a reduction in energy at the 2nd stage to 500 J in the midline and 250 J laterally; there were 4 injuries among 19 2nd stage procedures (21.1%). The overall incidence of mucosal injury, including stage 3 and 4 procedures, was therefore 42.6%; 37% of these were “occult” (only visualized endoscopically). CONCLUSIONS AND SIGNIFICANCE: RFAP, although intended to be mucosa-sparing, is nevertheless associated with a high incidence of mucosal injuries, many of which are occult. The occurrence of these mucosal ulcers is usually associated with only a trivial degree of increased pain postoperatively.
Hepatic hydrothorax: case report and literature review

Hepatic hydrothorax is a rare complication that occurs in patients with liver cirrhosis. We report the case of a patient with NASH cirrhosis and evidence of portal hypertension who was admitted to the emergency department with coughing and chest pain. Transudative pleural effusions (according to Light's criteria) were found in association with ascites, but no cardiac cause, pleural effusion or pulmonary effusion could be found. Treatment with diuretics was begun, but was suspended because the patient developed signifi cant renal dys- function. Fluid was drained with a thoracostomy but additional loss of fl uid led to further deterioration of renal function. It was decided to insert a transjugular portosystemic shunt (TIPS) to signifi cantly decrease portal pressure and to progressively decrease ascitic fl uid and pleural effusion. A subsequent review of the patient and radiological follow-up found no recurrence of symptoms, pleural effusion or ascites.
Inflammation, vitamin D and dendritic cell precursors in chronic kidney disease

Decreased blood dendritic cell precursors (DCP) count is linked with atherosclerotic disease, while reduction of circulating DCP is also seen in patients with chronic kidney disease (CKD). As poor vitamin D status could be linked to a compromised innate immune response, we hypothesized that vitamin D status might be involved in the decrease in circulating DCP in CKD. Moreover, the potential role of inflammation was considered. Circulating myeloid (mDCP), plasmacytoid (pDCP) and total DCP (tDCP) were analysed using flow cytometry in 287 patients with CKD stage 3. Serum 25(OH)D and 1,25(OH)2D levels were measured using enzyme‐linked immunosorbent assays (ELISA), interleukin (IL)‐6, IL‐10 and tumour necrosis factor (TNF)‐α using cytometric bead array, C‐reactive protein (CRP) using a high‐sensitivity (hs) ELISA. Contrary to our hypothesis, there was no association between vitamin D levels and DCP, although their number was decreased significantly in CKD (P < 0·001). Instead, mDCP (r = −0·211) and tDCP (r = −0·188,) were associated slightly negatively with hsCRP but positively with the estimated glomerular filtration rate (eGFR, r = 0·314 for tDCP). According to multivariate linear regression, only higher hsCRP concentration and the presence of diabetes mellitus had a significant negative influence on DCP count (P < 0·03, respectively) but not vitamin D, age and eGFR. A significant impact of vitamin D on the reduction of circulating DCP in CKD 3 patients can be neglected. Instead, inflammation as a common phenomenon in CKD and diabetes mellitus had the main influence on the decrease in DCP. Thus, a potential role for DCP as a sensitive marker of inflammation and cardiovascular risk should be elucidated in future studies.
Post‐ and prejunctional consequences of ecto‐ATPase inhibition: electrical and contractile studies in guinea‐pig vas deferens

At sites of purinergic neurotransmission, synaptic ecto‐ATPase is believed to limit the actions of ATP following its neural release. However, details of the modulation by this enzyme of the ATP‐mediated conductance change and the possible mechanisms mediating this modulation remain unelucidated. We have addressed these issues by studying the effect of ARL 67156, a selective ecto‐ATPase inhibitor, on ATP‐mediated electrical and contractile activity in the sympathetically innervated guinea‐pig vas deferens. ARL 67156 at 100 μm significantly potentiated the amplitude of spontaneous excitatory junction potentials (SEJPs) by 81.1% (P < 0.01) and prolonged their time courses (rise time by 49.7%, decay time constant by 38.2%; P < 0.01). Moreover, the frequency of occurrence of SEJPs was strikingly increased (from 0.28 ± 0.13 to 0.90 ± 0.26 Hz; P < 0.01), indicating an additional, primarily presynaptic, effect of ecto‐ATPase inhibition. The frequency of occurrence of discrete events (DEs), which represent nerve stimulation‐evoked quantal release of neurotransmitter, was also increased (∼6‐fold; P < 0.01), along with the appearance of DEs at previously ‘silent’ latencies. Purinergic contractions of the vas deferens were potentiated significantly (P < 0.01) by ARL 67156; these potentiated contractions were suppressed by the A1 agonist adenosine (P < 0.01) but left unaffected by the A1 antagonist 8‐phenyltheophylline (8‐PT). Our results indicate (i) that ecto‐ATPase activity, in addition to modulating the ATP‐mediated postjunctional conductance change, may regulate transmitter release prejunctionally under physiological conditions, and (ii) that the prejunctional regulation may be mediated primarily via presynaptic P2X, rather than A1, receptors.
Indole-3-Acetic Acid Biosynthesis Is Deficient in Gluconacetobacter diazotrophicus Strains with Mutations in Cytochrome c Biogenesis Genes

ABSTRACT Gluconacetobacter diazotrophicus is an endophyte of sugarcane frequently found in plants grown in agricultural areas where nitrogen fertilizer input is low. Recent results from this laboratory, using mutant strains of G. diazotrophicus unable to fix nitrogen, suggested that there are two beneficial effects of G. diazotrophicus on sugarcane growth: one dependent and one not dependent on nitrogen fixation. A plant growth-promoting substance, such as indole-3-acetic acid (IAA), known to be produced by G. diazotrophicus, could be a nitrogen fixation-independent factor. One strain, MAd10, isolated by screening a library of Tn5 mutants, released only ∼6% of the amount of IAA excreted by the parent strain in liquid culture. The mutation causing the IAA− phenotype was not linked to Tn5. A pLAFR3 cosmid clone that complemented the IAA deficiency was isolated. Sequence analysis of a complementing subclone indicated the presence of genes involved in cytochrome c biogenesis (ccm, for cytochrome c maturation). The G. diazotrophicus ccm operon was sequenced; the individual ccm gene products were 37 to 52% identical to ccm gene products of Escherichia coli and equivalent cyc genes of Bradyrhizobium japonicum. Although several ccm mutant phenotypes have been described in the literature, there are no reports of ccm gene products being involved in IAA production. Spectral analysis, heme-associated peroxidase activities, and respiratory activities of the cell membranes revealed that the ccm genes of G. diazotrophicus are involved in cytochrome c biogenesis.
Serial and parallel processing in rhesus monkey auditory cortex

Auditory cortex on the exposed supratemporal plane in four anesthetized rhesus monkeys was mapped electrophysiologically with both pure‐tone (PT) and broad‐band complex sounds. The mapping confirmed the existence of at least three tonotopic areas. Primary auditory cortex, AI, was then aspirated, and the remainder of the cortex on the supratemporal plane was remapped. PT‐responses in the caudomedial area, CM, were abolished in all animals but one, in which they were restricted to the high‐frequency range. Some CM sites were still responsive to complex stimuli. In contrast to the effects on CM, no significant changes were detectable in the rostral area, R.
e-Business - An Online Shop in the Area of Technical and Scientific Publications

The explosive growth of the world-wide-web and the emergence of e-commerce enabled the development of recommender systems that became to an independent emerged research area in the mid-1990s. The recommender systems are used to solve the prediction problem or the top-N recommendation problem. However, recommendation systems feel ever more the pressure related to a change on users habits. In order to capture users interests it is necessary a representation of information about an individual user. Our Online Shop in the Area of Technical and Scientific Publications intends to add the best of the user-based collaborative filtering and content-based collaborative filtering methodologies into a single hybrid methodology in order to answer some issues raised about new users and new items added to the recommender system. And also try to combine inference and prediction to assist the user in finding content that is of personal interest or even combine data mining techniques to provide recommendations.
Research on the Ant—Administrative Monopoly and Promoting Competition of Natural Monopoly Industry

Natural monopoly can restrict competition and reduce the efficiency of industrial resource allocation.This paper analyzes the appearance and feature of natural monopoly industry and puts forward the remarkable feature of natural monopoly industry in our country is that natural monopoly and administrative monopoly exist at the same time,and then illustrates the reason why administrative monopoly can come along with natural monopoly and the harmfulness of administrative monopoly.Finally,this paper puts forward the measures of anti—administrative monopoly and promoting competition of natural monopoly industry in our country.
Joint stability characteristics of the ankle complex after lateral ligamentous injury, part I: a laboratory comparison using arthrometric measurement.

CONTEXT The mechanical property of stiffness may be important to investigating how lateral ankle ligament injury affects the behavior of the viscoelastic properties of the ankle complex. A better understanding of injury effects on tissue elastic characteristics in relation to joint laxity could be obtained from cadaveric study. OBJECTIVE To biomechanically determine the laxity and stiffness characteristics of the cadaver ankle complex before and after simulated injury to the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) during anterior drawer and inversion loading. DESIGN Cross-sectional study. SETTING University research laboratory. PATIENTS OR OTHER PARTICIPANTS Seven fresh-frozen cadaver ankle specimens. INTERVENTION(S) All ankles underwent loading before and after simulated lateral ankle injury using an ankle arthrometer. MAIN OUTCOME MEASURE(S) The dependent variables were anterior displacement, anterior end-range stiffness, inversion rotation, and inversion end-range stiffness. RESULTS Isolated ATFL and combined ATFL and CFL sectioning resulted in increased anterior displacement but not end-range stiffness when compared with the intact ankle. With inversion loading, combined ATFL and CFL sectioning resulted in increased range of motion and decreased end-range stiffness when compared with the intact and ATFL-sectioned ankles. CONCLUSIONS The absence of change in anterior end-range stiffness between the intact and ligament-deficient ankles indicated bony and other soft tissues functioned to maintain stiffness after pathologic joint displacement, whereas inversion loading of the CFL-deficient ankle after pathologic joint displacement indicated the ankle complex was less stiff when supported only by the secondary joint structures.
Timing of Childhood Immigration and Children's Life Chances

This article examines the relationship between the timing of childhood immigration and children’s life chances in adulthood. I analyze panel data on siblings from Norwegian administrative registries which enables me to disentangle the effect of age at arrival on adult socioeconomic outcomes from all fixed family-level conditions and endowments shared by siblings. Findings from sibling fixed-effects models reveal a progressively stronger adverse influence of immigration at later stages of childhood on children’s completed schooling, employment, adult earnings, occupational attainment, and social welfare assistance. The persistence of these relationships within families indicates that experiences related to the timing of childhood immigration have causal effects on later-life outcomes. The effect of age at arrival is heterogeneous across regions of origin. It is strong among childhood immigrants arriving from less-developed origin countries, but weak among children with background from developed countries. In sum, these findings indicate that the timing of childhood immigration after early-life formative periods can impose structural constraints on children’s human capital accumulation and labor market opportunities over the life course.
A non-intrusive load identification method based on convolution neural network

Load identification have shown significant performance gains in smart meters. Most existing load identification algorithms are based on electrical characteristics of steady or transient state, which are therefore limited by feature selection. In recent years, due to the strong self-learning capability of deep learning, it has been widely applied and has produced satisfactory results in many fields, but non-intrusive load monitoring (NILM) has seen few attempts. From the perspective of image processing, this paper uses the Convolution neural network (CNN) of deep learning to analyze the potential characteristics of the load current waveform. This work starts with building the current data set of different appliances' on and off states, and then the structure and parameter of CNN are designed based on current waveform features to identify the load. This method is simple to operate, and a series of experiment verify its feasibility and accuracy.
The Use of In Vivo, Ex Vivo, In Vitro, Computational Models and Volunteer Studies in Vision Research and Therapy, and Their Contribution to the Three Rs

Much is known about mammalian vision, and considerable progress has been achieved in treating many vision disorders, especially those due to changes in the eye, by using various therapeutic methods, including stem cell and gene therapy. While cells and tissues from the main parts of the eye and the visual cortex (VC) can be maintained in culture, and many computer models exist, the current non-animal approaches are severely limiting in the study of visual perception and retinotopic imaging. Some of the early studies with cats and non-human primates (NHPs) are controversial for animal welfare reasons and are of questionable clinical relevance, particularly with respect to the treatment of amblyopia. More recently, the UK Home Office records have shown that attention is now more focused on rodents, especially the mouse. This is likely to be due to the perceived need for genetically-altered animals, rather than to knowledge of the similarities and differences of vision in cats, NHPs and rodents, and the fact that the same techniques can be used for all of the species. We discuss the advantages and limitations of animal and non-animal methods for vision research, and assess their relative contributions to basic knowledge and clinical practice, as well as outlining the opportunities they offer for implementing the principles of the Three Rs (Replacement, Reduction and Refinement).
The organization of olivo‐cerebellar projections in the opossum, Didelphis Virginiane, as revealed by the retrograde transport of horseradish peroxidase

The retrograde transport of horseradish peroxidase was utilized to map olivo‐cerebellar projections in the Virginia opossum. The spinal cerebellum (anterior lobe, paramedian lobule and pyramis) receive input from several separate regions in the dorsal accessory nucleus, the medial accessory nucleus and portions of the principal nucleus. Evidence is present for a topographical organization whereby specific regions of the olive project to restricted longitudinal zones. The visual‐auditory region of the posterior vermis receives input from small areas within the caudal part of the medial accessory nucleus. From a distinctly separate region of the caudal part of the medial accesssory nucleus (as well as the principle nucleus), axons project to the uvula. The vestibulo‐cerebellum is the recipient of axons from the cap of Kooy and from two spatially separate regions of the medial accessory nucleus. The cerebellar hemisphere(Crus I and II, lobus simplex) is the target of axons from the different nuclei are targeted upon separate zones. The paraflocculus was found to receive an input from the rostral part of the medial accessory nucleus and from the principal nucleus.