Miracle-dz/UniFAR-FTUs huggingface dataset:
Silencing and Activation of Embryonic Globin Gene Expression

Abstract: An understanding of the mechanisms that control developmental stage‐specific transcription of globin genes offers the promise of successful therapeutic activation of fetal or embryonic β‐type genes in β‐thalassemia syndromes. A large body of evidence supports the notion of conservation of such mechanisms across vertebrate species and validates the use of pre‐clinical studies of silencing and activation of fetal or embryonic globin genes in animals. Using globin gene transfections into primary avian erythroid cells and cultured murine erythroleukemia cells, we have studied mechanisms involved in stage‐specific embryonic β‐type globin gene silencing and activation. These studies show that 1) methylation of the exact CpG nucleotides that are methylated in normal adult erythroid cells in vivo is capable of blocking transcription of a transfected embryonic globin gene promoter via binding of a methyl DNA binding protein in primary erythroid cells. 2) Activation of embryonic β‐type globin gene transcription in adult erythroid cells by short chain fatty acids is mediated through specific DNA sequences both in the promoter and downstream of the promoter.
Influence of slot and pole number combinations on unbalanced magnetic force in permanent magnet machines

Unbalanced magnetic forces (UMF) exist in permanent magnet machines having pole and slot numbers differed by one and two, even when there is no rotor eccentricity. In machines having pole and slot numbers differed by two, the on-load UMF results only when the single layer winding is employed and the number of coils is odd. This paper investigates the influence of slot and pole number combinations on the UMF. UMF may be divided into two components due to the radial and tangential traveling force waves. It is found that they are additive for machines having a pole pair number p=3k+1, e.g. 8-pole/9-slot and 8-pole/6-slot, but cancelling for machines having p=3k−1, e.g. 16-pole/15-slot and 16-pole/18-slot. Further, due to the additive and cancelling effects, for the same slot number, the machine having a smaller pole number exhibits larger UMF when the slot/pole numbers differ by one, while the machine having a larger pole number exhibits larger UMF when the slot/pole numbers differ by two and the slot number is higher than 6. For the same pole number, machines having slot/pole numbers differed by two exhibit smaller UMF than machines having slot/pole numbers differed by one. It is also found that if p=3k−1, the UMF gradually diminishes to 0 with the increase of pole number. On the other hand, when p=3k+1, it reduces to a certain value with the increase of pole number. The experimental results verify the predictions.
Spatial diversity in mitochondrial cytochrome c oxidase in house flies

Abstract. DNA sequence analysis at mitochondrial gene COI was surveyed in 293 house flies, Musca domestica Linneaus (Diptera: Muscidae), in 29 populations from North, Central and South America, Europe, Asia, Africa, and the Western Pacific. Nei's gene diversity index (HS) was 0.47, the chance that two randomly chosen flies have different COI haplotypes. Haplotype diversity was greater in the Old World (HS = 0.58) than the New World (HS = 0.31). The hierarchical partition of the total diversity indicated substantial differentiation at all levels (GST = 0.30), and highly structured populations. All pairwise estimates of gene flow between zoogeographical regions were less than 0.70 reproducing females per generation. The results are compared to those of a similar study based on the single‐strand conformation polymorphism method. Probable colonization scenarios for house flies into the New World are discussed and it is concluded that house flies are a recent addition to the fauna of the Western Hemisphere.
Optimizing signal‐to‐noise ratio of high‐resolution parallel single‐shot diffusion‐weighted echo‐planar imaging at ultrahigh field strengths

The potential signal‐to‐noise ratio (SNR) gain at ultrahigh field strengths offers the promise of higher image resolution in single‐shot diffusion‐weighted echo‐planar imaging the challenge being reduced T2 and T2* relaxation times and increased B0 inhomogeneity which lead to geometric distortions and image blurring. These can be addressed using parallel imaging (PI) methods for which a greater range of feasible reduction factors has been predicted at ultrahigh field strengths—the tradeoff being an associated SNR loss. Using comprehensive simulations, the SNR of high‐resolution diffusion‐weighted echo‐planar imaging in combination with spin‐echo and stimulated‐echo acquisition is explored at 7 T and compared to 3 T. To this end, PI performance is simulated for coil arrays with a variable number of circular coil elements. Beyond that, simulations of the point spread function are performed to investigate the actual image resolution. When higher PI reduction factors are applied at 7 T to address increased image distortions, high‐resolution imaging benefits SNR‐wise only at relatively low PI reduction factors. On the contrary, it features generally higher image resolutions than at 3 T due to smaller point spread functions. The SNR simulations are confirmed by phantom experiments. Finally, high‐resolution in vivo images of a healthy volunteer are presented which demonstrate the feasibility of higher PI reduction factors at 7 T in practice. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Hypoxanthine, xanthine, and uric acid in newborn pigs during hypoxemia followed by resuscitation with room air or 100% oxygen

ObjectiveTo determine if resuscitation with room air is as effective as resuscitation with an Fio2 of 1.0. DesignProspective, randomized laboratory study. SettingExperimental laboratory (neonatal or delivery ward). SubjectsTwenty piglets, 1 to 2 wks of age. InterventionsPiglets were randomized into two groups. Both groups underwent hypoxemia for 2 hrs and then underwent reoxygenation for 1 hr (group 1 with an Fio2 of 1.0 and group 2 with an Fio2 of 0.21). Measurements and Main ResultsHypoxanthine, xanthine, uric acid, Pao2, oxygen saturation, pH, base excess or deficit, and arterial pressure. During hypoxemia (Pao2 26 to 49 torr [3.5 to 6.5 kPa]), the mean hypoxanthine concentrations increased (p < .02) from 26.1 to 115.4 μmol/L in plasma, from 20.9 to 81.7 μmol/L in cerebrospinal fluid, and from 12.9 to 21.5 μmol/L in vitreous humor. Xanthine concentrations changed in a similar way, whereas uric acid concentrations increased only in plasma.During reoxygenation, hypoxanthine concentrations increased both in cerebrospinal fluid and in the vitreous humor. Final concentrations in these two fluid areas were 81.8 and 39.4 μmol/L, respectively (p < .02). Xanthine concentrations increased similarly. In plasma, hypoxanthine and xanthine concentrations decreased during reoxygenation. The final mean concentration of hypoxanthine was 76.8 μmol/L (p < .02). No change in plasma or cerebrospinal fluid uric acid concentrations were found during reoxygenation. The other measurements varied throughout the experiment, but no differences were found between the groups. ConclusionsThere were no significant differences between the two treatment groups at any stage in the experiments. In this porcine model of hypoxemia, resuscitation with room air was as effective as was resuscitation with an Fio2 of 1.0, when circulating concentrations of oxypurines were used as an end-point.
Reduced glycosylation of human cell lines increases susceptibility to CD4-independent infection by human immunodeficiency virus type 2 (LAV-2/B)

The human immunodeficiency virus type 2 (HIV-2) strain LAV-2/B is able to infect a variety of human cell lines via a CD4-independent pathway. We have used the glycosylation inhibitors tunicamycin, swainsonine, and deoxymannojirimycin to further characterize this putative alternative receptor for HIV-2 (LAV-2/B). These antibiotics resulted in an increase (5- to 30-fold) in the susceptibility of a variety of CD4- human cell lines to infection by LAV-2/B (RD, HeLa, HT29, Rsb, Heb7a, Hos, and Daudi). Several nonprimate cell lines (mink Mv-1-lu, rabbit SIRC, hamster a23, mouse NIH 3T3, cat CCC, and rat HSN) remained resistant to infection by LAV-2/B after treatment with glycosylation inhibitors, suggesting that they do not express the HIV-2 CD4-independent receptor. Two of these nonprimate cell lines are readily infected by HIV-2 when they express CD4 (Mv-1-lu and CCC). Treatment of human cells with neuraminidase had no effect on subsequent infection by LAV-2/B, suggesting that the increase in susceptibility to infection of deglycosylated cells is not due to a change in the electrostatic charge of the cell surface. Treatment of RD CD4- cells and HeLa CD4+ cells with a variety of proteases resulted in a 75 to 90% decrease in infection by LAV-2/B when compared with untreated cells. Taken together, all these data suggest that HIV-2 can utilize a membrane glycoprotein other than CD4 to attach and fuse with a variety of human cells.
Beyond the Pixel-Wise Loss for Topology-Aware Delineation

Delineation of curvilinear structures is an important problem in Computer Vision with multiple practical applications. With the advent of Deep Learning, many current approaches on automatic delineation have focused on finding more powerful deep architectures, but have continued using the habitual pixel-wise losses such as binary cross-entropy. In this paper we claim that pixel-wise losses alone are unsuitable for this problem because of their inability to reflect the topological impact of mistakes in the final prediction. We propose a new loss term that is aware of the higher-order topological features of linear structures. We also exploit a refinement pipeline that iteratively applies the same model over the previous delineation to refine the predictions at each step, while keeping the number of parameters and the complexity of the model constant. When combined with the standard pixel-wise loss, both our new loss term and an iterative refinement boost the quality of the predicted delineations, in some cases almost doubling the accuracy as compared to the same classifier trained with the binary cross-entropy alone. We show that our approach outperforms state-of-the-art methods on a wide range of data, from microscopy to aerial images.
FGF‐23 and Osteoprotegerin but not Fetuin‐A are associated with death and enhance risk prediction in non‐dialysis chronic kidney disease stages 3–5.

Numerous biomarkers have been shown to associate with clinical endpoints in chronic kidney disease (CKD). There is limited evidence whether biomarkers improve risk prediction in relation to clinical outcomes. Our study investigates whether a small suite of key chronic kidney disease‐mineral and bone disorder biomarkers could be used to enhance risk assessment in CKD.
Autoimmune liver diseases and recurrence after orthotopic liver transplantation: what have we learned so far?

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) may all recur after liver transplant. Diagnosis of rPBC is defined by histology; rAIH by serology, biochemistry and histology; rPSC by histology and/or imaging of the biliary tree and exclusion of other causes of nonanastomotic biliary strictures. Criteria for recurrent disease (RD) may differ from those used in similar disease in the native liver: frequent use of immunosuppressive therapy changes the pattern and natural history of RD and can co‐exist with other transplant‐related causes of graft damage. RD may occur in the presence of normal liver tests; the reported incidence will depend on the way in which diagnostic tests (especially protocol biopsies) are applied. The risk of RD increases with time, but does not correlate with the rate of graft loss. Treatment is largely unproven: ursodeoxycholic acid will improve serology and may slow progression of rPSC and rPBC; introduction or increased dose of corticosteroids may reduce progression of rAIH. Risk factors for rPBC include use of tacrolimus compared with cyclosporine; for rPSC include absence of colon peri‐transplantation and for rAIH possible associations with some HLA haplotypes have been suggested.
Enhancing successful outcomes of wiki-based collaborative writing: a state-of-the-art review of facilitation frameworks

This state-of-the-art review research undertook a survey of a variety of studies regarding wiki-based collaborative writing projects and from this body of work extracted the best practices tenets of facilitation. Wiki-based collaborative writing projects are becoming more common in second language (L2) pedagogy. Such projects have multiple aims. These include, among other benefits, L2 acquisition, P2P learning, collaboration and immersion in new technologies that will inform the social and professional lives of the students. By mining a variety of wiki-based collaborative writing projects for the specific meta and secondary facilitation practices, the researchers were able to develop a general framework that will assist instructors of university or advanced high school students who wish to engage their students in such projects. The attributes of good facilitation that the researchers have isolated are by no means exhaustive, nor are they a guarantee of successful outcomes. These attributes do, however, provide a good starting point for any teacher or instructional designer who wants to provide an environment that fosters student satisfaction, motivation and learning.
Heterogeneity of Cingulate Contributions to Spatial Attention

Functional magnetic resonance imaging was used to investigate activation patterns within the cingulate region during tasks based on spatial attention. Subjects were asked to detect targets which appeared either at the site indicated by a cue or on the opposite side. A "cue effect" was identified by the presence of shorter reaction times to validly than invalidly cued targets, showing that an anticipatory bias had been generated in the direction of the cue. Target detection accuracy was consistently above 90% although cue effects and reaction times displayed substantial variations, from one task session to another. Activation within the anterior cingulate region was seen in 16 of the 26 sessions but showed no correlation with reaction time. Posterior cingulate activation was seen in only 6 of the 26 sessions. However, a random effects analysis showed that the task-related signal change in this region was strongly correlated with the speed of target detection. A post hoc analysis indicated that this correlation was significant only when cue effects were present. No other part of the cerebral cortex displayed significant correlations with reaction times or cue effects. These results suggest that the cingulate component of the attentional network has at least two functionally segregated sectors, an anterior one in BA 24/32 and a posterior cingulo-retrosplenial one in BA 23/29/30. The posterior sector appears to be associated with the speed of detecting spatial targets, especially when attention is under the influence of a cue-induced anticipatory bias. The anterior cingulate focus did not display such a relationship in our tasks and is likely to mediate other aspects of attentional deployment such as performance monitoring, response selection or target identification.
Automated Detection of Sepsis Using Electronic Medical Record Data: A Systematic Review

Abstract: Severe sepsis and septic shock are global issues with high mortality rates. Early recognition and intervention are essential to optimize patient outcomes. Automated detection using electronic medical record (EMR) data can assist this process. This review describes automated sepsis detection using EMR data. PubMed retrieved publications between January 1, 2005 and January 31, 2015. Thirteen studies met study criteria: described an automated detection approach with the potential to detect sepsis or sepsis-related deterioration in real or near-real time; focused on emergency department and hospitalized neonatal, pediatric, or adult patients; and provided performance measures or results indicating the impact of automated sepsis detection. Detection algorithms incorporated systemic inflammatory response and organ dysfunction criteria. Systems in nine studies generated study or care team alerts. Care team alerts did not consistently lead to earlier interventions. Earlier interventions did not consistently translate to improved patient outcomes. Performance measures were inconsistent. Automated sepsis detection is potentially a means to enable early sepsis-related therapy but current performance variability highlights the need for further research.
Enhanced Permeability of Insulin across the Rat Intestinal Membrane by Various Absorption Enhancers: Their Intestinal Mucosal Toxicity and Absorption‐enhancing Mechanism of n‐Lauryl‐β‐D‐maltopyranoside

We have examined the in‐vitro permeability characteristics of insulin in the presence of various absorption enhancers across rat intestinal membranes and have assessed the intestinal toxicity of the enhancers using an in‐vitro Ussing chamber method. The absorption enhancing mechanism of n‐lauryl‐β‐D‐maltopyranoside was studied also.
Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab.

PURPOSE Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy. PATIENTS AND METHODS Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses. RESULTS In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P = .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005), and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02). CONCLUSION The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.
Intraocular penetration of periocular ketorolac and efficacy in experimental uveitis.

PURPOSE To determine in rabbits whether periocular injection of ketorolac tromethamine effectively delivers the drug to the eye and, if so, whether this is efficacious in the treatment of experimental uveitis. METHODS Ketorolac was administered by anterior subconjunctival injection, posterior periocular injection, intramuscular injection, or topical eye drops. The aqueous and vitreous were assayed for ketorolac. Anterior subconjunctival and topical ketorolac were compared to control as well as topical and anterior subconjunctival steroid treatments in uveitis induced by the intravitreal injection of tumor necrosis factor. RESULTS Anterior subconjunctival injection led to high, though short-lived, levels of drug in the aqueous and vitreous. Posterior periocular injection led to much lower levels. Topical dosing led to relatively low aqueous and undetectable vitreous levels. No ocular levels were detected after intramuscular dosing. All tested antiinflammatory treatments were similarly effective in controlling uveitis. CONCLUSIONS Anterior subconjunctival injection of ketorolac produced high intraocular concentrations of drug and was beneficial in controlling the inflammation in this animal model of uveitis.
The effect of monochromatic aberrations on Autoref R‐1 readings

The Canon Autoref R‐1 is used extensively to investigate aspects of the accommodation response of the human eye. The measurement zone of the Autoref R‐1 is known to lie outside the central pupil and the instrument's readings are therefore potentially influenced by the monochromatic aberrations of the eye. Since these aberrations are known to change as a function of accommodation, the error associated with the aberrations might influence the stimulus–response slope. We used masks and contact lenses with known amounts of spherical aberration to establish the region of the pupil used by the Autoref R‐1 in deriving a reading of the refractive power of the eye. This region was estimated to be narrowly centred on a 3.5‐mm diameter. The spherical aberration of the eye was measured for five subjects across a range of accommodation levels and used to predict the likely effect upon Autoref R‐1 readings. Positive spherical aberration will result in an apparent lead of accommodation, while negative spherical aberration causes an apparent lag of accommodation. For eyes with normal levels of spherical aberration, the slope of the stimulus–response will appear to be marginally flatter when measured with the Autoref R‐1. An example of an eye with coma‐like aberrations is also shown to produce Autoref R‐1 results that will differ significantly from more central refractive measurements.
The contribution of social cognition in predicting social participation following moderate and severe TBI in youth

ABSTRACT Youth with moderate or severe traumatic brain injury (TBI) are at risk for reduced social participation after the injury, and the contribution of social cognition to these changes in functioning has been little studied. This study aimed to examine social participation and to measure the contribution of social and non-social cognitive functions to social participation impairment in youth (ages 12–21) who sustained moderate or severe TBI. Youth with TBI (n = 23) were compared to typically developing (TD) controls on self- and parent-rated social participation questionnaires. Direct testing of social cognition (mentalising, social knowledge, emotion recognition) and higher order cognitive abilities (intellectual abilities, attention and executive functions) was also conducted. Significant differences were found between the TBI participants and TD controls on social participation measures. Mentalising and problem-solving abilities revealed to be significant correlates of social participation as reported by youth with brain-injury and their parents. Overall, these results corroborate previous findings by showing that social participation is significantly reduced after TBI, and further shows that mentalising, which is not always considered during rehabilitation, is an important contributing factor. In addition to executive function measures, social cognition should therefore be systematically included in assessment following youth TBI for intervention and prevention purposes.