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Fedushko, Solomiia, Taras Ustyianovych, Yuriy Syerov, and Tomas Peracek. "User-Engagement Score and SLIs/SLOs/SLAs Measurements Correlation of E-Business Projects Through Big Data Analysis." Applied Sciences 10, no. 24 (December 20, 2020): 9112. http://dx.doi.org/10.3390/app10249112.
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The Covid-19 crisis lockdown caused rapid transformation to remote working/learning modes and the need for e-commerce-, web-education-related projects development, and maintenance. However, an increase in internet traffic has a direct impact on infrastructure and software performance. We study the problem of accurate and quick web-project infrastructure issues/bottleneck/overload identification. The research aims to achieve and ensure the reliability and availability of a commerce/educational web project by providing system observability and Site Reliability Engineering (SRE) methods. In this research, we propose methods for technical condition assessment by applying the correlation of user-engagement score and Service Level Indicators (SLIs)/Service Level Objectives (SLOs)/Service Level Agreements (SLAs) measurements to identify user satisfaction types along with the infrastructure state. Our solution helps to improve content quality and, mainly, detect abnormal system behavior and poor infrastructure conditions. A straightforward interpretation of potential performance bottlenecks and vulnerabilities is achieved with the developed contingency table and correlation matrix for that purpose. We identify big data and system logs and metrics as the central sources that have performance issues during web-project usage. Throughout the analysis of an educational platform dataset, we found the main features of web-project content that have high user-engagement and provide value to services’ customers. According to our study, the usage and correlation of SLOs/SLAs with other critical metrics, such as user satisfaction or engagement improves early indication of potential system issues and avoids having users face them. These findings correspond to the concepts of SRE that focus on maintaining high service availability.
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Paik, Sehmi, Arunsri Brown, Cindy L. Munro, Cynthia Nau Cornelissen, and Todd Kitten. "The sloABCR Operon of Streptococcus mutans Encodes an Mn and Fe Transport System Required for Endocarditis Virulence and Its Mn-Dependent Repressor." Journal of Bacteriology 185, no. 20 (October 15, 2003): 5967–75. http://dx.doi.org/10.1128/jb.185.20.5967-5975.2003.
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ABSTRACT Streptococcus mutans belongs to the viridans group of oral streptococci, which is the leading cause of endocarditis in humans. The LraI family of lipoproteins in viridans group streptococci and other bacteria have been shown to function as virulence factors, adhesins, or ABC-type metal transporters. We previously reported the identification of the S. mutans LraI operon, sloABCR, which encodes components of a putative metal uptake system composed of SloA, an ATP-binding protein, SloB, an integral membrane protein, and SloC, a solute-binding lipoprotein, as well as a metal-dependent regulator, SloR. We report here the functional analysis of this operon. By Western blotting, addition of Mn to the growth medium repressed SloC expression in a wild-type strain but not in a sloR mutant. Other metals tested had little effect. Cells were also tested for aerobic growth in media stripped of metals then reconstituted with Mg and either Mn or Fe. Fe at 10 μM supported growth of the wild-type strain but not of a sloA or sloC mutant. Mn at 0.1 μM supported growth of the wild-type strain and sloR mutant but not of sloA or sloC mutants. The combined results suggest that the SloABC proteins transport both metals, although the SloR protein represses this system only in response to Mn. These conclusions are supported by 55Fe uptake studies with Mn as a competitor. Finally, a sloA mutant demonstrated loss of virulence in a rat model of endocarditis, suggesting that metal transport is required for endocarditis pathogenesis.
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Jarchow, Meghann E., Paul Formisano, Shane Nordyke, and Matthew Sayre. "Measuring longitudinal student performance on student learning outcomes in sustainability education." International Journal of Sustainability in Higher Education 19, no. 3 (March 5, 2018): 547–65. http://dx.doi.org/10.1108/ijshe-11-2016-0200.
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Purpose The purpose of this paper is to describe the student learning outcomes (SLOs) for a sustainability major, evaluate faculty incorporation of the SLOs into the courses in the sustainability major curriculum and measure student performance on the SLOs from entry into the major to the senior capstone course. Design/methodology/approach Through an iterative approach with a faculty advisory committee, SLOs were developed for the sustainability major. Curriculum mapping followed by evaluation of course syllabi were used to determine the extent to which each course addressed the SLOs. Student performance on most SLOs was measured through student assessment in an introductory and capstone course to evaluate the change in performance over time. Findings The core courses of the sustainability major were more likely to address the SLOs of the major than that of the elective courses. Where measured, student performance on the SLOs increased from the introductory course to the capstone course. Sustainability majors participated in an average of almost ten experiential learning opportunities focused on sustainability. Originality/value This research provides a longitudinal assessment of student learning in an undergraduate sustainability major. Because undergraduate sustainability degrees are generally new, this research can serve as a base upon which to continue to improve sustainability curriculum design.
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Gallois, Cindy, Peta Ashworth, Joan Leach, and Kieren Moffat. "The Language of Science and Social Licence to Operate." Journal of Language and Social Psychology 36, no. 1 (August 20, 2016): 45–60. http://dx.doi.org/10.1177/0261927x16663254.
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Social licence to operate (SLO) is an informal agreement that infers ongoing acceptance of an industrial or energy project by a local community and the stakeholders affected by it. Negotiation of SLOs centrally implicates language and communication, including scientific language and concepts. We first review the literature about the definition and communicative features of SLOs, and their relation to scientific communication. We describe communication accommodation theory and the ways that it can help understand (un)successful SLO negotiation, and describe examples of texts that show accommodative or nonaccommodative language around SLOs. We summarize some results which help indicate different ways of accommodating communities in the negotiation of SLOs. Finally, we describe a research agenda on communication accommodation and SLOs, in the service of improving their impact on energy, the environment, and the transfer of science.
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Pabbisetty, Sudheer K., Whitney Rabacal, Emmanuel J. Volanakis, Vrajesh V. Parekh, Danyvid Olivares-Villagómez, Delphine Cendron, Kelli L. Boyd, Luc Van Kaer, and Eric Sebzda. "Peripheral tolerance can be modified by altering KLF2-regulated Treg migration." Proceedings of the National Academy of Sciences 113, no. 32 (July 26, 2016): E4662—E4670. http://dx.doi.org/10.1073/pnas.1605849113.
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Tregs are essential for maintaining peripheral tolerance, and thus targeting these cells may aid in the treatment of autoimmunity and cancer by enhancing or reducing suppressive functions, respectively. Before these cells can be harnessed for therapeutic purposes, it is necessary to understand how they maintain tolerance under physiologically relevant conditions. We now report that transcription factor Kruppel-like factor 2 (KLF2) controls naive Treg migration patterns via regulation of homeostatic and inflammatory homing receptors, and that in its absence KLF2-deficient Tregs are unable to migrate efficiently to secondary lymphoid organs (SLOs). Diminished Treg trafficking to SLOs is sufficient to initiate autoimmunity, indicating that SLOs are a primary site for maintaining peripheral tolerance under homeostatic conditions. Disease severity correlates with impaired Treg recruitment to SLOs and, conversely, promotion of Tregs into these tissues can ameliorate autoimmunity. Moreover, stabilizing KLF2 expression within the Treg compartment enhances peripheral tolerance by diverting these suppressive cells from tertiary tissues into SLOs. Taken together, these results demonstrate that peripheral tolerance is enhanced or diminished through modulation of Treg trafficking to SLOs, a process that can be controlled by adjusting KLF2 protein levels.
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Terasaki, Hiroto, Shozo Sonoda, Masatoshi Tomita, and Taiji Sakamoto. "Recent Advances and Clinical Application of Color Scanning Laser Ophthalmoscope." Journal of Clinical Medicine 10, no. 4 (February 11, 2021): 718. http://dx.doi.org/10.3390/jcm10040718.
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Scanning laser ophthalmoscopes (SLOs) have been available since the early 1990s, but they were not commonly used because their advantages were not enough to replace conventional color fundus photography. In recent years, color SLOs have improved significantly, and the colored SLO images are obtained by combining multiple SLO images taken by lasers of different wavelengths. A combination of these images of different lasers can create an image that is close to that of the real ocular fundus. One advantage of the advanced SLOs is that they can obtain images with a wider view of the ocular fundus while maintaining a high resolution even through non-dilated eyes. The current SLOs are superior to the conventional fundus photography in their ability to image abnormal alterations of the retina and choroid. Thus, the purpose of this review was to present the characteristics of the current color SLOs and to show how that can help in the diagnosis and the following of changes after treatments. To accomplish these goals, we will present our findings in patients with different types of retinochoroidal disorders.
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Beilhack, Andreas, Stephan Schulz, Jeanette Baker, Georg F. Beilhack, Ryosei Nishimura, Enosh M. Baker, Gilad Landan, et al. "Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs." Blood 111, no. 5 (March 1, 2008): 2919–28. http://dx.doi.org/10.1182/blood-2007-09-112789.
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In acute graft-versus-host disease (aGVHD), donor T cells attack the recipient's gastrointestinal tract, liver, and skin. We hypothesized that blocking access to distinct lymphoid priming sites may alter the specific organ tropism and prevent aGVHD development. In support of this initial hypothesis, we found that different secondary lymphoid organs (SLOs) imprint distinct homing receptor phenotypes on evolving alloreactive effector T cells in vivo. Yet preventing T-cell entry to specific SLOs through blocking monoclonal antibodies, or SLO ablation, did not alter aGVHD pathophysiology. Moreover, transfer of alloreactive effector T cells into conditioned secondary recipients targeted the intestines and liver, irrespective of their initial priming site. Thus, we demonstrate redundancy of SLOs at different anatomical sites in aGVHD initiation. Only prevention of T-cell entry to all SLOs could completely abrogate the onset of aGVHD.
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Pfeffer, Bruce A., Libin Xu, and Steven J. Fliesler. "Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith–Lemli–Opitz Syndrome." International Journal of Molecular Sciences 22, no. 5 (February 26, 2021): 2339. http://dx.doi.org/10.3390/ijms22052339.
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Smith–Lemli–Opitz Syndrome (SLOS) results from mutations in the gene encoding the enzyme DHCR7, which catalyzes conversion of 7-dehydrocholesterol (7DHC) to cholesterol (CHOL). Rats treated with a DHCR7 inhibitor serve as a SLOS animal model, and exhibit progressive photoreceptor-specific cell death, with accumulation of 7DHC and oxidized sterols. To understand the basis of this cell type specificity, we performed transcriptomic analyses on a photoreceptor-derived cell line (661W), treating cells with two 7DHC-derived oxysterols, which accumulate in tissues and bodily fluids of SLOS patients and in the rat SLOS model, as well as with CHOL (negative control), and evaluated differentially expressed genes (DEGs) for each treatment. Gene enrichment analysis and compilation of DEG sets indicated that endoplasmic reticulum stress, oxidative stress, DNA damage and repair, and autophagy were all highly up-regulated pathways in oxysterol-treated cells. Detailed analysis indicated that the two oxysterols exert their effects via different molecular mechanisms. Changes in expression of key genes in highlighted pathways (Hmox1, Ddit3, Trib3, and Herpud1) were validated by immunofluorescence confocal microscopy. The results extend our understanding of the pathobiology of retinal degeneration and SLOS, identifying potential new druggable targets for therapeutic intervention into these and other related orphan diseases.
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Plakht, Ygal, Dan Greenberg, Harel Gilutz, Jonathan Eli Arbelle, and Arthur Shiyovich. "Associations between Subsequent Hospitalizations and Primary Ambulatory Services Utilization within the First Year after Acute Myocardial Infarction and Long-Term Mortality." Journal of Clinical Medicine 9, no. 8 (August 5, 2020): 2528. http://dx.doi.org/10.3390/jcm9082528.
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Healthcare resource utilization peaks throughout the first year following acute myocardial infarction (AMI). Data linking the former and outcomes are sparse. We evaluated the associations between subsequent length of in-hospital stay (SLOS) and primary ambulatory visits (PAV) within the first year after AMI and long-term mortality. This retrospective analysis included patients who were discharged following an AMI. Study groups: low (0–1 days), intermediate (2–7) and high (≥8 days) SLOS; low (<10) and high (≥10 visits) PAV, throughout the first post-AMI year. All-cause mortality was set as the primary outcome. Overall, 8112 patients were included: 55.2%, 23.4% and 21.4% in low, intermediate and high SLOS groups respectively; 26.0% and 74.0% in low and high-PAV groups. Throughout the follow-up period (up to 18 years), 49.6% patients died. Multivariable analysis showed that an increased SLOS (Hazard ratio (HR) = 1.313 and HR = 1.714 for intermediate and high vs. low groups respectively) and a reduced number of PAV (HR = 1.24 for low vs. high groups) were independently associated with an increased risk for mortality (p < 0.001 for each). Long-term mortality following AMI is associated with high hospital and low primary ambulatory services utilization throughout the first-year post-discharge. Measures focusing on patients with increased SLOS and reduced PAV should be considered to improve patient outcomes.
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Marsh, Patricia A., and Dennis L. Poepsel. "Perceived Usefulness of Learning Outcomes Predicts Ratings of Departmental Helpfulness." Teaching of Psychology 35, no. 4 (October 2008): 335–42. http://dx.doi.org/10.1080/00986280802374245.
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Psychology seniors at a Midwest university reflected on the student learning outcomes (SLOs) for the major. This study examined the relations among students' perceived usefulness of the SLOs, measures of learning, ratings of self-confidence in their knowledge of psychology, and evaluations of the department's helpfulness in students' skill development. Correlations showed few significant relations between usefulness of the SLOs and measures of learning and no relations with ratings of self-confidence. Perceived usefulness of the outcomes was a significant predictor of the department's perceived helpfulness in students' skill development. However, students' perceptions of the department dropped significantly by the end of the capstone course. We discuss implications related to activities teachers might use to enhance learning.
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Mitra, Anjali, Shelley Dolitsky, Stacy Yadava, and Elena Ashkinadze. "Smith–Lemli–Opitz's Syndrome as a Possible Cause of Recurrent Pregnancy Loss: A Case Report." American Journal of Perinatology Reports 10, no. 01 (January 2020): e118-e120. http://dx.doi.org/10.1055/s-0040-1705131.
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AbstractBased on the known carrier frequency of Smith–Lemli–Opitz's syndrome (SLOS), the prevalence of this disease should be significantly higher than what is observed in the population. This may be due to a higher rate of pregnancy loss in affected embryos. Here, we present the case of a couple who underwent expanded carrier screening (ECS) after experiencing three first trimester pregnancy losses. Both parents were found to be carriers of SLOS mutations, and DNA analysis of the fetal remains of the third loss revealed the aborted fetus had inherited both the maternal and paternal mutations. This suggests SLOS as a reason for this patient's recurrent pregnancy loss (RPL), and therefore, ECS should be considered as part of the RPL work-up.
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Song, Danni, Anne Loyle-Langholz, Jeanne L. Higbee, and Zhou Zhou. "Achieving Course Objectives And Student Learning Outcomes: Seeking Student Feedback On Their Progress." Contemporary Issues in Education Research (CIER) 6, no. 3 (June 27, 2013): 289. http://dx.doi.org/10.19030/cier.v6i3.7898.
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Most postsecondary faculty in the UnitedStates include course goals or objectives as key components of their syllabi. In addition to individual course objectives, manyinstitutions have identified institution-wide student learning outcomes(SLOs). This paper describes one facultymembers attempts to elicit feedback from students regarding their growthrelated to both course objectives and SLOs and provides the results from acourse evaluation and a focus group.
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Shoemaker, Candice A. "Student Confidence as a Measure of Learning in an Undergraduate Principles of Horticultural Science Course." HortTechnology 20, no. 4 (August 2010): 683–88. http://dx.doi.org/10.21273/horttech.20.4.683.
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Three to five student learning outcomes (SLOs) were written for each of seven units for the Principles of Horticultural Science course, the foundation course for all nine specializations within the undergraduate horticulture program at Kansas State University. The SLOs were then used as the framework for development of the course. A pre- and post-assessment was given to the students enrolled in the course in the fall semesters of 2005 through 2008 in an effort to assess if the SLOs were being met. The 50-item assessment asked students to record their confidence in ability to do something reflective of the SLOs such as “distinguish between transpiration and respiration” or “write a scientific plant name.” The comparison of the student-reported confidence at the start of the course and their academic performance in the course were not correlated. Students' reported confidence at the conclusion of the course was correlated with their academic performance in 3 of the 4 years that were examined. Because confidence was correlated with academic performance in the course and a course would be considered a domain-specific construct, it is more likely that self-efficacy rather than confidence was impacted as the students moved through the course.
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Maehara, Takashi, Hamid Mattoo, Vinay S. Mahajan, Samuel JH Murphy, Grace J. Yuen, Noriko Ishiguro, Miho Ohta, et al. "The expansion in lymphoid organs of IL-4+ BATF+ T follicular helper cells is linked to IgG4 class switching in vivo." Life Science Alliance 1, no. 1 (January 2018): e201800050. http://dx.doi.org/10.26508/lsa.201800050.
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Distinct T follicular helper (TFH) subsets that influence specific class-switching events are assumed to exist, but the accumulation of isotype-specific TFH subsets in secondary lymphoid organs (SLOs) and tertiary lymphoid organs has not been hitherto demonstrated. IL-4–expressing TFH cells are surprisingly sparse in human SLOs. In contrast, in IgG4-related disease (IgG4-RD), a disorder characterized by polarized Ig class switching, most TFH cells in tertiary and SLOs make IL-4. Human IL-4+ TFH cells do not express GATA-3 but express nuclear BATF, and the transcriptomes of IL-4–secreting TFH cells differ from both PD1hi TFH cells that do not secrete IL-4 and IL-4–secreting non-TFH cells. Unlike IgG4-RD, IL-4+ TFH cells are rarely found in tertiary lymphoid organs in Sjögren’s syndrome, a disorder in which IgG4 is not elevated. The proportion of CD4+IL-4+BATF+ T cells and CD4+IL-4+CXCR5+ T cells in IgG4-RD tissues correlates tightly with tissue IgG4 plasma cell numbers and plasma IgG4 levels in patients but not with the total plasma levels of other isotypes. These data describe a disease-related TFH subpopulation in human tertiary lymphoid organs and SLOs that is linked to IgG4 class switching.
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Donoghue, Sarah E., James J. Pitt, Avihu Boneh, and Susan M. White. "Smith-Lemli-Opitz syndrome: clinical and biochemical correlates." Journal of Pediatric Endocrinology and Metabolism 31, no. 4 (March 28, 2018): 451–59. http://dx.doi.org/10.1515/jpem-2017-0501.
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AbstractBackground:Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in theDHCR7gene that result in reduced cholesterol biosynthesis. The aim of the study was to examine the biochemical and clinical features of SLOS in the context of the emerging evidence of the importance of cholesterol in morphogenesis and steroidogenesis.Methods:We retrospectively reviewed the records of 18 patients (including four fetuses) with confirmed SLOS and documented their clinical and biochemical features.Results:Seven patients had branchial arch abnormalities, including micrognathia, immune dysfunction and hypocalcemia. Thymic abnormalities were found in three fetuses. All four patients with a cholesterol level of ≤0.35 mmol/L died. They all had electrolyte abnormalities (hyperkalemia, hyponatremia, hypocalcemia), necrotizing enterocolitis, sepsis-like episodes and midline defects including the branchial and cardiac defects. Patients with cholesterol levels ≥1.7 mmol/L had milder features and were diagnosed at 9 months to 25 years of age. All 10 patients had intellectual disability. One patient was found to have a novel mutation, c.1220A>G (p.Asn407Ser).Conclusions:We suggest that screening for adrenal insufficiency and for hypoparathyroidism, hypothyroidism and immunodeficiency, should be done routinely in infants diagnosed early with SLOS. Early diagnosis and intervention to correct these biochemical consequences may decrease mortality and improve long-term outcome in these patients.
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SAHİTO, Nasreen. "EVALUATING THE NATIONAL CURRICULUM OF COMPUTER SCIENCE GRADE 6 TO 8 BY USING BLOOM’S TAXONOMY." IJAEDU- International E-Journal of Advances in Education 5, no. 15 (December 28, 2019): 361–69. http://dx.doi.org/10.18768/ijaedu.593884.
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Critical thinking, problem solving and logical reasoning are considered as the 21st century learning skills. These higher order thinking skills (HOTS) can only be developed through curriculum and teaching and learning strategies, because it include critical, logical, reflective, metacognitive, and creative thinking. The purpose of this study is to analyze National Curriculum 2006 (Pakistan) of Computer Education in order to observe that how much it is helpful for the development of higher order thinking skills among the students and whether it has focused on merging 21st century interdisciplinary themes with core contents of the subject. The National Curriculum2006 (Pakistan) of Computer Education from grade VI to VIII was analyzed using the revised blooms taxonomy. Out of six levels, upper three levels Analyzing, Evaluating and Creating were considered as HOTS. Frequency and Proportions were calculated for Student Learning Outcomes (SLOs) meeting HOTS criteria. P21 framework was used for checking the contents and SLOs which merging the 21st century interdisciplinary themes in curriculum. Overall only 9% of the SLOs in curriculum met the requirement of HOTS. There was a slightly increasing trend was observed from grade 6 to 8. Grade 6 had 6%, grade 7 had 9% and grade 8 had 11% of HOTS. However overall proportion of SLOs meeting HOTS was low but an increasing trend was observed from grade VI to grade VIII. In order to develop HOTS among the students, there is a need to redesign the curriculum, teachers should be trained accordingly and assessment standards should also be meeting with curriculum needs. It will help in the re-designing of National Curriculum for Computer Education Grade VI-VIII. This study can be expended to analyze the National Curriculum for other subjects. Keywords Higher Order Thinking Skills, Curriculum, SLOs, 21st century skills, Critical Thinking
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Reddy, Uma, George Saade, Robert Goldenberg, Donald Dudley, Corette Parker, Vanessa Thorsten, Halit Pinar, et al. "Smith–Lemli–Opitz Mutations in Unexplained Stillbirths." American Journal of Perinatology 35, no. 10 (February 12, 2018): 936–39. http://dx.doi.org/10.1055/s-0038-1626705.
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Objective Smith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by a defect in cholesterol biosynthesis with mutations in 7-dehydrocholesterol reductase (DHCR7). A total of 3% of Caucasians carry DHCR7 mutations, theoretically resulting in a homozygote frequency of 1/4000. However, SLOS occurs in only 1/20,000 to 60,000 live births. Our objective was to assess DHCR7 mutations in unexplained stillbirths. Study Design Prospective, multicenter, population-based case–control study of all stillbirths and a representative sample of live births enrolled in five geographic areas. Cases with stillbirth due to obstetric complications, infection, or aneuploidy, and those with poor quality deoxyribonucleic acid (DNA) were excluded. DNA was extracted from placental tissue stored at –80°C, and exons 3 to 9 of the DCHR7 gene were amplified, purified, and subjected to bidirectional sequencing to identify mutations. Results One-hundred forty four stillbirths were unexplained and had adequate DNA for analysis. Nine stillbirths of 139 (6.5%) had a single mutation in one allele in coding exons 3 to 9 of DHCR7 (Table 1). One case (0.7%) was a compound heterozygote for mutations in exons 3 to 9 of DHCR7; this fetus had no clinical or histologic features of SLOS. Conclusion We detected SLOS mutations in only 0.7% of stillbirths. This does not support a strong association between unrecognized DHCR7 mutations and stillbirth.
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Berteloot, Laureline, Thierry Jo Molina, Julie Bruneau, Capucine Picard, Vincent Barlogis, Véronique Secq, Chrystelle Abdo, et al. "Alternative pathways for the development of lymphoid structures in humans." Proceedings of the National Academy of Sciences 118, no. 29 (July 14, 2021): e2108082118. http://dx.doi.org/10.1073/pnas.2108082118.
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Lymphoid tissue inducer (LTi) cells are critical for inducing the differentiation of most secondary lymphoid organs (SLOs) in mice. In humans, JAK3 and γc deficiencies result in severe combined immunodeficiency (SCIDs) characterized by an absence of T cells, natural killer cells, innate lymphoid cells (ILCs), and presumably LTi cells. Some of these patients have undergone allogeneic stem cell transplantation (HSCT) in the absence of myeloablation, which leads to donor T cell engraftment, while other leukocyte subsets are of host origin. By using MRI to look for SLOs in nine of these patients 16 to 44 y after HSCT, we discovered that SLOs were exclusively found in the three areas of the abdomen that drain the intestinal tract. A postmortem examination of a child with γc-SCID who had died 3.5 mo after HSCT showed corticomedullary differentiation in the thymus, T cell zones in the spleen, and the appendix, but in neither lymph nodes nor Peyer patches. Tertiary lymphoid organs were observed in the lung. No RAR-related orphan receptor-positive LTi cells could be detected in the existing lymphoid structures. These results suggest that while LTi cells are required for the genesis of most SLOs in humans, SLO in the appendix and in gut-draining areas, as well as tertiary lymphoid organs, can be generated likely by LTi cell-independent mechanisms.
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Baig, Sana, Fareeha Javed, Aishah Siddiquah, and Afifa Khanam. "A Content Analysis of English Textbook of Punjab Textbook Board of Grade 8 in Pakistan." SAGE Open 11, no. 2 (April 2021): 215824402110231. http://dx.doi.org/10.1177/21582440211023159.
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The present study analyzes the English textbook of Grade 8 published by Punjab Textbook Board in Pakistan in the light of student learning outcomes (SLOs) of four competencies: reading and thinking skills, writing skills, oral communication skills, and formal and lexical aspects of language of the latest English curriculum in Pakistan. Competency (C), standards (S), benchmarks (B), and SLOs are the parameters given in the National Curriculum. A semi-structured checklist was developed by the researchers, validated by three experts from the relevant field, and improved in the light of experts’ opinion and pilot study findings. To evaluate the textbook competencies and their SLOs, the evidence was sought from the textbook, and remarks were given in the last column (remarks/analysis) of the checklist. The results revealed that the textbook understudy focuses on reading comprehension only. There is thus a dire need to incorporate thinking skills, writing skills, oral/aural communication skills, and formal and lexical aspects of language in the textbook.
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Brown, Charles, Farzad Sekhavati, Ruben Cardenes, Claudia Windmueller, Karma Dacosta, Jaime Rodriguez-Canales, and Keith E. Steele. "CTLA-4 Immunohistochemistry and Quantitative Image Analysis for Profiling of Human Cancers." Journal of Histochemistry & Cytochemistry 67, no. 12 (October 14, 2019): 901–18. http://dx.doi.org/10.1369/0022155419882292.
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There is an important need in immuno-oncology to develop reliable immunohistochemistry (IHC) to assess the expression of CTLA-4+ tumor-infiltrating lymphocytes in human cancers and quantify them with image analysis (IA). We used commercial polyclonal and monoclonal antibodies and characterized three chromogenic cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) assays with suitable specificity and sensitivity for use in formalin-fixed, paraffin-embedded (FFPE) tissues. We found variable numbers of CTLA-4+ lymphocytes in multiple types of cancer and secondary lymphoid organs (SLOs) and other normal human tissues. Combining CTLA-4 with CD3, CD4, or CD8 by immunofluorescence showed that CTLA-4+ lymphocytes in SLOs and tumors were typically CD3+ and CD4+, but not CD8+. Individual lymphocytes expressed CTLA-4 either as primarily granular cytoplasmic staining or as excentric globular deposits. The CTLA-4/FoxP3 (forkhead box P3 protein) duplex IHC demonstrated that CTLA-4+/FoxP3− lymphocytes predominated in the germinal centers of SLOs and tumor tertiary lymphoid structures (TLSs), whereas CTLA-4+/FoxP3+ lymphocytes populated the T-cell zone of SLOs and TLSs, plus tumor stroma. IA scoring was highly comparable with pathologist scoring for CTLA-4 and CTLA-4/FoxP3 assays and a FoxP3 single IHC. Our findings show that CTLA-4 IHC can be used to reliably label lymphocytes in FFPE human tissues, making it possible to investigate the role of CTLA-4 in the tumor microenvironment.
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Лазаревич, А. А., И. В. Новикова, С. О. Мясников, Н. А. Венчикова, Э. И. Мараховская, and Т. А. Плевако. "Smith-Lemli-Opitz syndrome in the fetus of the second trimester of pregnancy with a predominant involvement skeletal system." Nauchno-prakticheskii zhurnal «Medicinskaia genetika», no. 8(217) (August 31, 2020): 78–79. http://dx.doi.org/10.25557/2073-7998.2020.08.78-79.
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Приведено описание спорадического случая синдрома Смита-Лемли-Опитца (СЛОС) у плода второго триместра. Основные ультразвуковые признаки были сходны с синдромом коротких ребер-полидактилии. Нозологический диагноз установлен при молекулярно-генетическом исследовании. Обсуждаются и сопоставляются нетипичные проявления СЛОС с данными литературы. We present a sporadic case of Smith-Lemli-Opitz syndrome (SLOS) in the fetus of the second trimester. The ultrasound (US) signs were similar to the syndrome of short ribs-polydactyly (SCRP). The diagnosis was established by molecular genetic testing. The atypical manifestations of SLOS are discussed and compared with literature data.
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Cook, Sophie R., Cerys Bladen, Johanna Smith, Emily Maguire, Jordan Copner, Gareth D. Fenn, Kim Wager, Helen Waller-Evans, and Emyr Lloyd-Evans. "Visualisation of cholesterol and ganglioside GM1 in zebrafish models of Niemann–Pick type C disease and Smith–Lemli–Opitz syndrome using light sheet microscopy." Histochemistry and Cell Biology 154, no. 5 (October 20, 2020): 565–78. http://dx.doi.org/10.1007/s00418-020-01925-2.
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AbstractLysosomal storage diseases are the most common cause of neurodegeneration in children. They are characterised at the cellular level by the accumulation of storage material within lysosomes. There are very limited therapeutic options, and the search for novel therapies has been hampered as few good small animal models are available. Here, we describe the use of light sheet microscopy to assess lipid storage in drug and morpholino induced zebrafish models of two diseases of cholesterol homeostasis with lysosomal dysfunction: First, Niemann–Pick type C disease (NPC), caused by mutations in the lysosomal transmembrane protein NPC1, characterised by intralysosomal accumulation of cholesterol and several other lipids. Second, Smith–Lemli–Opitz syndrome (SLOS), caused by mutations in 7-dehydrocholesterol reductase, which catalyses the last step of cholesterol biosynthesis and is characterised by intralysosomal accumulation of dietary cholesterol. This is the first description of a zebrafish SLOS model. We find that zebrafish accurately model lysosomal storage and disease-specific phenotypes in both diseases. Increased cholesterol and ganglioside GM1 were observed in sections taken from NPC model fish, and decreased cholesterol in SLOS model fish, but these are of limited value as resolution is poor, and accurate anatomical comparisons difficult. Using light sheet microscopy, we were able to observe lipid changes in much greater detail and identified an unexpected accumulation of ganglioside GM1 in SLOS model fish. Our data demonstrate, for the first time in zebrafish, the immense potential that light sheet microscopy has in aiding the resolution of studies involving lysosomal and lipid disorders.
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Griffiths, William J., Yuqin Wang, Kersti Karu, Emmanuel Samuel, Shane McDonnell, Martin Hornshaw, and Cedric Shackleton. "Potential of Sterol Analysis by Liquid Chromatography–Tandem Mass Spectrometry for the Prenatal Diagnosis of Smith-Lemli-Opitz Syndrome." Clinical Chemistry 54, no. 8 (August 1, 2008): 1317–24. http://dx.doi.org/10.1373/clinchem.2007.100644.
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Abstract Background: Smith-Lemli-Opitz syndrome (SLOS), a severe disorder of cholesterol synthesis, is classically diagnosed prenatally by GC-MS analysis of sterols in amniotic fluid. Considering the current trend toward tandem mass spectrometry (MS/MS) methodologies, we developed prototype LC-MS/MS methods for accurate diagnosis of the disorder. Methods: 3β-Hydroxysterols in amniotic fluid are oxidized with cholesterol oxidase to their corresponding 3-ketones, which are then derivatized with Girard P (GP) hydrazine in a “one-pot” reaction. The resulting GP-hydrazones give an improved response in electrospray (ES)–MS/MS owing to the presence of a charged quaternary nitrogen and are analyzed by reversed-phase LC-ES-MS/MS. Both capillary and conventional LC-MS/MS formats are suitable, and the method is also applicable to paper-absorbed blood spots. Results: In a double-blind analysis of 18 amniotic fluid samples comprising 6 SLOS and 12 controls, the ratio of 7 + 8-dehydrocholesterol (7 + 8-DHC) to cholesterol was <0.02 [range 0.00–0.02, mean (SD) 0.01 (0.007)] in all control samples (intraassay variation 5.91%) and >0.20 [0.20–1.13, 0.79 (0.35)] in SLOS (intraassay variation 4.56%), corresponding to a difference in ratios between the 2 groups of at least a factor of 10. The limit of quantification was equivalent to that of 2 nL amniotic fluid injected on-column. Conclusions: We describe a proof-of-concept for the prenatal diagnosis of SLOS. Further developments will be necessary to automate sample handling and reduce chromatographic time for the methodology to be used in pre- and postnatal diagnosis.
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Knoll, Benjamin R. "Learning by Doing: Mentoring Group-Based Undergraduate Research Projects in an Upper-Level Political Science Course." PS: Political Science & Politics 49, no. 01 (January 2016): 128–31. http://dx.doi.org/10.1017/s1049096515001146.
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ABSTRACTUndergraduate research (UGR) is a “high-impact practice” that has been consistently shown to effectively promote desirable student-learning outcomes (SLOs) including critical thinking, logic, written and oral communication, problem solving, and interpretation of evidence, especially among minority and disadvantaged students. Mentoring quality UGR experiences in regular upper-level political science courses, however, is a difficult and time-consuming activity. This article describes an attempt to provide an intensive, semester-long, and group-based UGR experience in an upper-level American politics course. It discusses how this experience was designed to deliberately foster specific institutional UGR SLOs and summarizes student perceptions of the overall effectiveness of the experience.
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Beilhack, Andreas, Stephan Schulz, Jeanette Baker, Georg F. Beilhack, Ryosei Nishimura, Gilad Landan, Enosh M. Baker, Edward I. Herman, Christopher H. Contag, and Robert S. Negrin. "A Signal Hierarchy Model of Alloreactive T Cell Trafficking for the Organ Manifestation in Acute Graft-Versus-Host Disease." Blood 108, no. 11 (November 16, 2006): 72. http://dx.doi.org/10.1182/blood.v108.11.72.72.
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Abstract Acute graft-versus-host disease (aGVHD) is caused by alloreactive effector T cells attacking the gastrointestinal tract, liver and skin after allogeneic hematopoietic cell transplantation (aHCT). The mechanism by which alloreactive T cells target these organs and not others remains elusive. Recently, we reported that different secondary lymphoid organs (SLOs), as alloreactive priming sites, can imprint distinct homing phenotypes on evolving alloreactive effector cells in vivo. However, preventing access to selected lymphoid organs (via the use of blocking antibodies or recipient mice lacking Peyer’s patches (PP), PP and lymph nodes (LN) or spleens) did not alter the aGVHD organ manifestation. These findings not only suggested a high redundancy of SLOs as induction sites of aGVHD, but also questioned whether homing instruction of alloreactive T cells by these sites can explain the mechanism of aGVHD target organ manifestation. To test the homing instruction model we transplanted transgenic luciferase+ (luc+) FVB/N (H-2q, Thy1.1+) splenocytes into conditioned (2×400rad) Balb/c recipients (H-2d, Thy1.2+). On day+3 we isolated luc+ donor lymphocytes from peripheral LN, mesenteric LN, or spleens and transferred them into conditioned secondary allogeneic recipients. 16 hours later, bioluminescence imaging revealed that allogeneic luc+ T cells irrespective of their original priming site targeted the intestinal tract and liver. Subsequently, we compared aHCT of conditioned with non-conditioned secondary Balb/cRag−/− cγ-Chain−/− recipients. Surprisingly, we found allogeneic luc+ T cells accumulating in SLOs in non-conditioned recipients in contrast to intestinal and hepatic tissues in conditioned recipients. These in vivo findings establish that alloreactive effector cells migrate to aGVHD target tissues because of attraction to these sites rather than specific instruction by SLOs. Therefore, we propose a signal hierarchy model of alloreactive cell trafficking whereby inflammatory signal/ligand interactions dominate over organ-specific homing receptor/ligand interactions.
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Yasuda, Takuwa, Taku Kuwabara, Hideki Nakano, Kentaro Aritomi, Takashi Onodera, Martin Lipp, Yousuke Takahama, and Terutaka Kakiuchi. "Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells." Blood 109, no. 2 (September 14, 2006): 449–56. http://dx.doi.org/10.1182/blood-2006-04-018101.
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Abstract Secondary lymphoid organs (SLOs) provide a niche for the initiation and regulation of T-cell responses, but the mechanisms have been poorly understood. We investigated the influence of chemokines CCL19 and CCL21 constitutively expressed in SLOs on activation-induced cell death (AICD) of CD4+ T cells. When paucity of lymph node T cells (plt) mutant mice lacking expression of CCL19/CCL21 were primed with OVA/CFA, both expansion of OVA-responding CD4+ T cells in the draining lymph nodes and an in vitro recall response were prolonged as compared with responses in wild-type (WT) mice. The apoptotic cell frequency among OVA-responding CD4+ T cells was similarly low in plt/plt and WT mice during the clonal expansion phase. However, during the clonal contraction phase, the frequency never increased in plt/plt mice, whereas in WT mice it continuously increased to a peak 18 days after immunization. The presence of CCL19/CCL21 during the in vitro stimulation of CD4+ T cells with anti-CD3 plus anti-CD28 significantly enhanced in vitro AICD induction of the restimulated T cells, partially through enhancing expression of Fas ligand. Our results suggest that CCL19/CCL21 produced by stromal cells and antigen-presenting cells regulate CD4+ T-cell immune responses in SLOs by promoting AICD.
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Srivastava, Saurabh, Natallia Makarava, Elizaveta Katorcha, Regina Savtchenko, Reinhard Brossmer, and Ilia V. Baskakov. "Post-conversion sialylation of prions in lymphoid tissues." Proceedings of the National Academy of Sciences 112, no. 48 (November 16, 2015): E6654—E6662. http://dx.doi.org/10.1073/pnas.1517993112.
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Sialylated glycans on the surface of mammalian cells act as part of a “self-associated molecular pattern,” helping the immune system to recognize “self” from “altered self” or “nonself.” To escape the host immune system, some bacterial pathogens have evolved biosynthetic pathways for host-like sialic acids, whereas others recruited host sialic acids for decorating their surfaces. Prions lack nucleic acids and are not conventional pathogens. Nevertheless, prions might use a similar strategy for invading and colonizing the lymphoreticular system. Here we show that the sialylation status of the infectious, disease-associated state of the prion protein (PrPSc) changes with colonization of secondary lymphoid organs (SLOs). As a result, spleen-derived PrPSc is more sialylated than brain-derived PrPSc. Enhanced sialylation of PrPSc is recapitulated in vitro by incubating brain-derived PrPSc with primary splenocytes or cultured macrophage RAW 264.7 cells. General inhibitors of sialyltranserases (STs), the enzymes that transfer sialic acid residues onto terminal positions of glycans, suppressed extrasialylation of PrPSc. A fluorescently labeled precursor of sialic acid revealed ST activity associated with RAW macrophages. This study illustrates that, upon colonization of SLOs, the sialylation status of prions changes by host STs. We propose that this mechanism is responsible for camouflaging prions in SLOs and has broad implications.
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Kovarova, Martina, Christopher A. Wassif, Sandra Odom, Katherine Liao, Forbes D. Porter, and Juan Rivera. "Cholesterol deficiency in a mouse model of Smith-Lemli-Opitz syndrome reveals increased mast cell responsiveness." Journal of Experimental Medicine 203, no. 5 (April 17, 2006): 1161–71. http://dx.doi.org/10.1084/jem.20051701.
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Mutation of the 3β-hydroxysterol Δ7-reductase gene (Dhcr7−/−) results in Smith-Lemli-Opitz syndrome (SLOS). Patients, and genetically altered mice, are unable to produce cholesterol and accumulate 7-dehydrocholesterol (DHC) in serum and tissue. This causes multiple growth and developmental abnormalities as well as immune system anomalies including allergy. Because cholesterol is a key component of liquid-ordered membranes (lipid rafts) and these domains have been implicated in regulating mast cell activation, we examined whether mast cell responsiveness is altered in this model. Mast cells derived from Dhcr7−/− mice (DHCR KO) showed constitutive cytokine production and hyper-degranulation after stimulation of the high affinity IgE receptor (FcεRI). DHCR KO mast cells, but not wild-type mast cells, accumulated DHC in lipid rafts. DHC partially disrupted lipid raft stability and displaced Lyn kinase protein and activity from lipid rafts. This led to down-regulation of some Lyn-dependent signaling events but increased Fyn kinase activity and Akt phosphorylation. The Lyn-dependent phosphorylation of Csk-binding protein, which negatively regulates Fyn activity, was decreased. This phenotype reproduces some of the characteristics of Lyn-null mast cells, which also demonstrate hyper-degranulation. These findings provide the first evidence of lipid raft dysfunction in SLOS and may explain the observed association of allergy with SLOS.
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Halin, Cornelia, M. Lucila Scimone, Roberto Bonasio, Jean-Marc Gauguet, Thorsten R. Mempel, Elizabeth Quackenbush, Richard L. Proia, Suzanne Mandala, and Ulrich H. von Andrian. "The S1P-analog FTY720 differentially modulates T-cell homing via HEV: T-cell–expressed S1P1 amplifies integrin activation in peripheral lymph nodes but not in Peyer patches." Blood 106, no. 4 (August 15, 2005): 1314–22. http://dx.doi.org/10.1182/blood-2004-09-3687.
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AbstractSphingosine-1-phosphate (S1P) and its receptor S1P1 control T-cell egress from thymus and secondary lymphoid organs (SLOs). To further define the role of S1P1 in lymphocyte trafficking, we performed adoptive transfer experiments and intravital microscopy (IVM) using both S1P1–/– lymphocytes and recipient wild-type (WT) mice treated with FTY720, an immunosuppressant that downmodulates S1P receptors. S1P1 deficiency and FTY720 caused rapid disappearance of T cells from blood, prolonged retention in SLOs, and accumulation in bone marrow, but did not alter interstitial T-cell motility in peripheral lymph nodes (PLNs) as assessed by multiphoton IVM. However, S1P1–/– lymphocytes displayed reduced short-term homing to PLNs due to attenuated integrin-mediated firm arrest in high endothelial venules (HEVs). By contrast, S1P1–/– T cells homed normally to Peyer patches (PPs), whereas S1P1–/– B cells had a marked defect in homing to PPs and arrested poorly in PP HEVs. Therefore, S1P1 not only controls lymphocyte egress from SLOs, but also facilitates in a tissue- and subset-specific fashion integrin activation during homing. Interestingly, FTY720 treatment enhanced accumulation of both S1P1 sufficient and S1P1–/– T cells in PPs by enhancing integrin-mediated arrest in HEVs. Thus, FTY720 exerts unique effects on T-cell traffic in PPs that are independent of T-cell–expressed S1P1.
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Lang, Willis, Srinath Shankar, Jignesh M. Patel, and Ajay Kalhan. "Towards Multi-Tenant Performance SLOs." IEEE Transactions on Knowledge and Data Engineering 26, no. 6 (June 2014): 1447–63. http://dx.doi.org/10.1109/tkde.2013.74.
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Shaikh, Muhammad, Maria Ulbrich, Juan Gamboa Vargas, Katja J. Ottmüller, Duc Dung Le, Zeinab Mokthari, Joern Pezoldt, et al. "Non-Hematopoietic Lymphoid Stromal Cells Prime Alloreactive CD4+ T Cells in Acute Graft-Versus-Host Disease." Blood 134, Supplement_1 (November 13, 2019): 4421. http://dx.doi.org/10.1182/blood-2019-125665.
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Allogeneic T cell priming is considered as an essential event determining the outcome of allogeneic hematopoietic stem cell transplantation (allo-HCT), ideally triggering anti-leukemic responses (GvL effect) or, at worst, causing life-threatening acute graft-versus-host disease (aGvHD). During acute GvHD initiation, alloreactive T cells are activated by host antigen presenting cells (APCs), rapidly expand and subsequently exert tissue damage. Recently, it was discovered that absence of host hematopoietic APCs does not prevent acute GvHD, suggesting a crucial role of non-hematopoietic APCs for priming alloreactive T cells (Toubai et al., Blood 2012, Li et al., J Immunol. 2012). Furthermore, it was even suggested that in the absence of professional APCs allogeneic CD4+ T cells can be activated in the lamina propria by MHC class II expressing myofibroblasts (Koyama et al., Nat Med 2012). As exact location and identity of host non-hematopoietic APCs triggering alloreactive T cell responses are essential to dissect the priming of GvHD-inducing vs. GvL-mediating allogeneic T cells, we investigated the role of lymph node stromal cells (LNSCs) in the initiation phase of aGvHD and their potential role as non-hematopoietic APCs. Employing allo-HCT mouse models in combination with flow cytometry and advanced microscopy techniques, we explored early alloreactive T cells activation first in a myeloablatively conditioned MHC major mismatch allo-HCT setting (FVB→B6). Under these conditions, CD4+ and CD8+ T cells activation and proliferation occurred exclusively in secondary lymphoid organs (SLOs) and not in the intestinal lamina propria early after allo-HCT within the first three days after allo-HCT. To study non-hematopoietic antigen presentation early after allo-HCT, we generated bone marrow B6.MHCIIΔ/Δ→B6.WT chimeras that lacked MHC II expression in the host hematopoietic compartment. Subsequent allo-HCT of these chimeras revealed activation and expansion of allogenic donor CD4+ T-cells exclusively in SLOs and not the lamina propria in the first three days after transplantation. Next, we generated recipient mice that selectively lacked MHCII expression either in CD11c expressing cells or under the control of the Vav1-promoter in all hematopoietic cells. In both type of recipients, allogenic donor CD4+ T-cells were activated within 3 days after allo-HCT in SLOs and no other tissues. After irradiation of B6.WT mice we observed LNSCs upregulate co-stimulatory receptors early after irradiation (24 and 72 hours), in vitro and in vivo suggesting that they may act as active non-hematopoietic APCs. Next, we performed mixed lymphocyte reactions (MLRs) of irradiated APCs derived from TgVav1-Cre+MHCIIΔ/Δmice with alloreactive CD4+ T cells from FVB mice. Here, we observed in the total absence of hematopoietic MHCII antigen presentation reduced but still pronounced activation of alloreactive CD4+ T cells. Therefore, in these transgenic allo-HCT models, hematopoietic cells in the SLOs were dispensable for alloreactive CD4+ T cell activation in the initiation phase of aGvHD. To ascertain that SLOs are the exclusive priming sites of alloreactive CD4+ T cells, we transplanted mesenteric lymph nodes (mLNs) from a B6.CD11c.DTR mice, depleted of CD11c+ cells into B6.MHCIIΔ/Δmice. After successful engraftment of donor mLNs in these mice, allo-HCT revealed these as unique priming sites in MHCII deficient hosts for alloreactive CD4+ T cells, which differentiated into CD44hiCD62Llow effector T cells that were detectable in the transplanted mLNs. Conclusively, these results indicate that specialized non-hematopoietic lymph node stromal cells prime alloreactive CD4+ T cell within the SLOs early after allo-HCT. Pinpointing the molecular pathways in these non-hematopoietic APCs within SLOs that trigger alloreactive T cell responses may prove fruitful for selective therapeutic intervention after allo-HCT. Disclosures No relevant conflicts of interest to declare.
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Lee, Ryan W. Y., and Elaine Tierney. "Hypothesis: The Role of Sterols in Autism Spectrum Disorder." Autism Research and Treatment 2011 (2011): 1–7. http://dx.doi.org/10.1155/2011/653570.
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A possible role for sterols in the development of autism spectrum disorder (ASD) has not been proven, but studies in disorders of sterol biosynthesis, chiefly Smith-Lemli-Opitz syndrome (SLOS), enable hypotheses on a causal relationship to be discussed. Advances in genetic technology coupled with discoveries in membrane physiology have led to renewed interest for lipids in the nervous system. This paper hypothesizes on the role of sterol dysfunction in ASD through the framework of SLOS. Impaired sonic hedgehog patterning, alterations in membrane lipid rafts leading to abnormal synaptic plasticity, and impaired neurosteroid synthesis are discussed. Potential therapeutic agents include the development of neuroactive steroid-based agents and enzyme-specific drugs. Future investigations should reveal the specific mechanisms underlying sterol dysfunction in neurodevelopmental disorders by utilizing advanced imaging and molecular techniques.
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Koczok, Katalin, László Horváth, Zeljka Korade, Zoltán András Mezei, Gabriella P. Szabó, Ned A. Porter, Eszter Kovács, Károly Mirnics, and István Balogh. "Biochemical and Clinical Effects of Vitamin E Supplementation in Hungarian Smith-Lemli-Opitz Syndrome Patients." Biomolecules 11, no. 8 (August 17, 2021): 1228. http://dx.doi.org/10.3390/biom11081228.
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Smith-Lemli-Opitz syndrome (SLOS) is a severe monogenic disorder resulting in low cholesterol and high 7-dehydrocholesterol (7-DHC) levels. 7-DHC-derived oxysterols likely contribute to disease pathophysiology, and thus antioxidant treatment might be beneficial because of high oxidative stress. In a three-year prospective study, we investigated the effects of vitamin E supplementation in six SLOS patients already receiving dietary cholesterol treatment. Plasma vitamin A and E concentrations were determined by the high-performance liquid chromatography (HPLC) method. At baseline, plasma 7-DHC, 8-dehydrocholesterol (8-DHC) and cholesterol levels were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS) method. The clinical effect of the supplementation was assessed by performing structured parental interviews. At baseline, patients were characterized by low or low–normal plasma vitamin E concentrations (7.19–15.68 μmol/L), while vitamin A concentrations were found to be normal or high (1.26–2.68 μmol/L). Vitamin E supplementation resulted in correction or significant elevation of plasma vitamin E concentration in all patients. We observed reduced aggression, self-injury, irritability, hyperactivity, attention deficit, repetitive behavior, sleep disturbance, skin photosensitivity and/or eczema in 3/6 patients, with notable individual variability. Clinical response to therapy was associated with a low baseline 7-DHC + 8-DHC/cholesterol ratio (0.2–0.4). We suggest that determination of vitamin E status is important in SLOS patients. Supplementation of vitamin E should be considered and might be beneficial.
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Fliesler, Steven, and Libin Xu. "Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention." Molecules 23, no. 10 (October 22, 2018): 2720. http://dx.doi.org/10.3390/molecules23102720.
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Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive human disease caused by mutations in the gene encoding 7-dehydrocholesterol (7DHC) reductase (DHCR7), resulting in abnormal accumulation of 7DHC and reduced levels of cholesterol in bodily tissues and fluids. A rat model of the disease has been created by treating normal rats with the DHCR7 inhibitor, AY9944, which causes progressive, irreversible retinal degeneration. Herein, we review the features of this disease model and the evidence linking 7DHC-derived oxysterols to the pathobiology of the disease, with particular emphasis on the associated retinal degeneration. A recent study has shown that treating the rat model with cholesterol plus suitable antioxidants completely prevents the retinal degeneration. These findings are discussed with regard to their translational implications for developing an improved therapeutic intervention for SLOS over the current standard of care.
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Pfund, Rory A., John C. Norcross, Robin Hailstorks, Karen E. Stamm, and Peggy Christidis. "Introduction to Psychology." Teaching of Psychology 45, no. 3 (May 31, 2018): 213–19. http://dx.doi.org/10.1177/0098628318779257.
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A robust literature has explored multiple facets of the introductory psychology course, but few studies have examined its purposes, student learning outcomes (SLOs), and assessment practices. The second iteration of the Undergraduate Study in Psychology gathered data on these facets in a nationally representative sample of associate ( n = 62) and baccalaureate psychology programs ( n = 161). Most department chairs indicated that their intro course served as both an introduction to the major and a general education function. Approximately one third of programs incorporated the American Psychological Association Guidelines for the Undergraduate Psychology Major 2.0 in their entirety or with minor changes to develop their SLOs for the introductory course. Written assignments and professor-developed quizzes/exams were the most frequently used assessment methods. Discussion centers on how these results may be used by teachers of introductory psychology.
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Iurian, Sorin Ioan, Livia Ognean, Han Brunner, Leo Kluijtmans, Petr Jira, Dana Fintina, and Bogdan Ionut Mehedintu. "SMITH-LEMLI-OPITZ SYNDROME. CASE REPORT." Romanian Journal of Pediatrics 64, no. 1 (March 31, 2015): 34–37. http://dx.doi.org/10.37897/rjp.2015.1.7.
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Smith-Lemli-Opitz syndrome (SLOS) is an autosomal-recessive inherited disease characterized by multiple anomalies secondary to cholesterol synthesis impairment. The authors present diagnosis peculiarities and limitation of treatment options in a 5-weeks old infant with ambiguous genitalia.
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Skarke, C. "Getting to the Root of SLOS." Science Translational Medicine 4, no. 142 (July 11, 2012): 142ec122. http://dx.doi.org/10.1126/scitranslmed.3004563.
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Wang, Chong, Lei Jin, Fan Qiao, Qing Xue, Xin Guan Zhang, and Lin Han. "Performance of The Society of Thoracic Surgeons 2008 Cardiac Risk Models for Major Postoperative Complications after Heart Valve Surgery in a Chinese Population: A Multicenter Study." Heart Surgery Forum 21, no. 4 (June 19, 2018): E281—E285. http://dx.doi.org/10.1532/hsf.1945.
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Background: To evaluate the performance of Society of Thoracic Surgeons (STS) 2008 cardiac surgery risk scores for postoperative complications in Chinese patients undergoing single valve surgery at multicenter institutions.
Methods: From January 2009 through December 2012, 4493 consecutive patients older than 16 years who underwent single valve surgery at 4 cardiac surgical centers were collected and scored according to the STS 2008 risk scores. The final research population included the following isolated heart valve surgery types: aortic valve replacement, mitral valve replacement, and mitral valve repair. Calibration of the risk scores was assessed by the Hosmer–Lemeshow (H-L) test. Discrimination was tested by calculating the area under the receiver operating characteristic (ROC) curve.
Results: The observed incidence rate for cerebrovascular accident (CVA), renal failure (RF), prolonged ventilation (Vent), reoperation (Reop), prolonged postoperative length of stay (PLOS), and short postoperative LOS (SLOS) was 0.90%, 1.32%, 4.18%, 2.43%, 3.64%, and 1.65%, respectively. The predicted incidence rate for CVA, RF, Vent, Reop, PLOS, and SLOS was 0.76%, 1.55%, 4.94%, 6.69%, 3.92%, and 2.54%, respectively. The STS 2008 risk scores give an accurate calibration for individual postoperative risk in CVA, RF, Vent, and PLOS (Hosmer–Lemeshow: P = .052, P = .474, P = .468, and P = .712, respectively). The area under the ROC curve of the STS 2008 risk scores for the above 4 postoperative complications were 0.714, 0.724, 0.727%, and 0.713, respectively.
Conclusion: The STS 2008 risk scores were suitable for major postoperative complications in patients undergoing single valve surgery, except for Reop and SLOS.
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Baig, Sana, Aishah Siddiquah, and Fareeha Javed. "An Analysis of the Competency Reading and Thinking Skills in Grade VIII English Textbook." Volume V Issue I V, no. I (March 30, 2020): 231–40. http://dx.doi.org/10.31703/gssr.2020(v-i).24.
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This research aimed at analysing the Grade VIII English textbook of Punjab Textbook Board against one of the five competencies, the Reading and Thinking skills and identifying the satisfaction level of Grade 8 students with their textbook for the fulfilment of this competency. The main parameters of the content analysis were Competency (C), Standards (S), Benchmarks (B) and SLOs. The data was collected through content analysis (of the textbook) and survey questionnaire. The student satisfaction level was measured with the help of an instrument comprising 10 statements on a 5-point Likert scale. The questionnaire respondents were 1440 students of Grade VIII studying in public schools of Lahore. The results of content analysis and student survey showed that the textbook partly meets the requirements related to the selected competency. It is therefore recommended that the English textbook of grade VIII should be updated in congruence with the SLOs of the selected competency.
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Atteberry, Allison, and Sarah E. LaCour. "Making a Tough Choice: Teacher Target-Setting and Student Achievement in a Teacher Performance System Using Student Learning Objectives." AERA Open 7 (January 2021): 233285842097977. http://dx.doi.org/10.1177/2332858420979778.
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The use of student learning objectives (SLOs) as part of teacher performance systems has gained traction quickly in the United States, yet little is known about how teachers select specific students’ learning goals. When teachers are evaluated—and sometimes compensated—based on whether their students meet the very objectives the teachers set at the start of the year, there may be an incentive to set low targets. SLO systems rely on teachers’ willingness and ability to set appropriately ambitious SLOs. We describe teachers’ SLO target-setting behavior in one school-district. We document the accuracy/ambitiousness of targets and find that teachers regularly set targets that students did not meet. We also find that, within the same year, a student’s spring test scores tend to be higher on the assessments for which they received higher targets. This raises the intriguing possibility that receiving higher targets might cause students to perform better than they otherwise would have.
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Tang, Bo, Xue Li, Yuanlin Liu, Xiuhui Chen, Ximei Li, Yanan Chu, Heng Zhu, et al. "The Therapeutic Effect of ICAM-1-Overexpressing Mesenchymal Stem Cells on Acute Graft-Versus-Host Disease." Cellular Physiology and Biochemistry 46, no. 6 (2018): 2624–35. http://dx.doi.org/10.1159/000489689.
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Background/Aims: Mesenchymal stem cells (MSCs) do not readily migrate to appropriate sites, and this creates a major obstacle for their use in the treatment of graft-versus-host disease (GVHD). Intercellular adhesion molecule-1 (ICAM-1) can guide the homing of various immune cells to the proper anatomical location within secondary lymphoid organs (SLOs), which are the major niches for generating immune responses or tolerance. MSCs rarely migrate to SLOs after intravenous infusion, and are constitutively low expression of ICAM-1. So in our previous work, ICAM-1 was engineered into a murine MSC line C3H10T1/2 by retrovirus transfection system (ICAM-1MSCs). Here, we hypothesized that ICAM-1highMSCs may significantly improve their immunomodulatory effect. Methods: We used different co-culture methods combined with real-time PCR and flow cytometry to evaluate ICAM-1highMSCs immunomodulatory effect on dendritic cells (DCs) and T cells in vitro and in vivo. MSCs were labeled with carboxyfluorescein diacetate succinimidylester (CFSE) to detect its distribution in mouse model. Results: Our in vitro analyses revealed ICAM-1 MSCs could suppress DCs maturation according to co-culture methods and suppress the T cell immune response according to the mixed lymphocyte response (MLR) and lymphoblast transformation test (LTT) tests. We found that infusion of ICAM-1highMSCs potently prolonged the survival of GVHD mouse model. The infused ICAM-1highMSCs migrate to SLOs in vivo, and suppressed DCs maturation, suppressed CD4+ T cell differentiation to Th1 cells, and increased the ratios of Treg cells. Conclusions: Taken together, these data demonstrate that ICAM-1highMSCs had an enhanced immunosuppressive effect on DCs and T cells, which may help explain the protective effect in a GVHD model. This exciting therapeutic strategy may improve the clinical efficacy of MSC-based therapy for GVHD.
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Mou, Fan, Maria Praskova, Fan Xia, Denille Van Buren, Hanno Hock, Joseph Avruch, and Dawang Zhou. "The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes." Journal of Experimental Medicine 209, no. 4 (March 12, 2012): 741–59. http://dx.doi.org/10.1084/jem.20111692.
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The Mst1 kinase is an important regulator of murine T cell adhesion, migration, proliferation, and apoptosis. In this study, we analyze mice lacking both Mst1 and Mst2 in hematopoietic cells. Compared with wild-type mice, these double knockout (DKO) mice exhibit a severe reduction in the number of mature T cells in the circulation and in secondary lymphoid organs (SLOs). CD4+CD8− and CD4−CD8+ single-positive (SP) thymocytes in DKO mice resemble mature T cells of wild-type mice but undergo excessive apoptosis, and their egress from the thymus is reduced by >90%. Even when placed directly in the circulation, DKO SP thymocytes failed to enter SLOs. In SP thymocytes, deficiency of Mst1 and Mst2 abolished sphingosine-1 phosphate– and CCL21-induced Mob1 phosphorylation, Rac1 and RhoA GTP charging, and subsequent cell migration. When phosphorylated by Mst1 or Mst2, Mob1 binds and activates the Rac1 guanyl nucleotide exchanger Dock8, which is abundant in the thymus. Thus, the Mst1 and Mst2 kinases control Rho GTPase activation and the migratory responses of SP thymocytes.
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Orellana, Julio Proaño, Blanca Caminero, Carmen Carrión, Luis Tomas, Selome Kostentinos Tesfatsion, and Johan Tordsson. "FPGA-Aware Scheduling Strategies at Hypervisor Level in Cloud Environments." Scientific Programming 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/4670271.
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Current open issues regarding cloud computing include the support for nontrivial Quality of Service-related Service Level Objectives (SLOs) and reducing the energy footprint of data centers. One strategy that can contribute to both is the integration of accelerators as specialized resources within the cloud system. In particular, Field Programmable Gate Arrays (FPGAs) exhibit an excellent performance/energy consumption ratio that can be harnessed to achieve these goals. In this paper, a multilevel cloud scheduling framework is described, and several FPGA-aware node level scheduling strategies (applied at the hypervisor level) are explored and analyzed. These strategies are based on the use of a multiobjective metric aimed at providing Quality of Service (QoS) support. Results show how the proposed FPGA-aware scheduling policies increment the number of users requests serviced with their SLOs fulfilled while energy consumption is minimized. In particular, evaluation results of a use case based on a multimedia application show that the proposal can save more than 20% of the total energy compared with other baseline algorithms while a higher percentage of Service Level Agreement (SLA) is fulfilled.
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Alluhaidan, Ala, and Evon M. Abu-Taieh. "Student Learning Outcomes (SLOs) and Assessment of Cybersecurity Body of Knowledge (BOK): Evaluation & Challenges." International Education Studies 13, no. 5 (March 21, 2020): 13. http://dx.doi.org/10.5539/ies.v13n5p13.
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The rapid growth of technology and related fields has led to creation in academia to match the expansion demand for IT professionals. One of the current majors that attract attention in industry is cybersecurity. There is a great need for individuals who are skilled in cybersecurity to protect IT infrastructure. Coaching a security-focused workforce has become the target of government agents, industry, and academic institutions.
As research and academic faculties respond to this growing demand, evolving curriculum and methodologies for teaching cybersecurity graduates still need to be formed comprehensively. There have been few researches to define and assess the student outcomes in cybersecurity. This paper presents a step forward by developing Student Learning Outcomes (SLOs) and the desired assessment method to measure those outcomes.
This research contributes to academia and training institution by defining the SLOs and suggests preferable assessment methods in cybersecurity. This initial research is based on a qualitative study of academician evaluation of cybersecurity courses. The paper presents the result of interviews along with discussions of ongoing and future suggestions.
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LITTLE, LINDA. "Consider SLOS in Children Presenting With Autism." Pediatric News 39, no. 6 (June 2005): 29. http://dx.doi.org/10.1016/s0031-398x(05)70303-9.
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Kitten, Todd, Cindy L. Munro, Suzanne M. Michalek, and Francis L. Macrina. "Genetic Characterization of a Streptococcus mutans LraI Family Operon and Role in Virulence." Infection and Immunity 68, no. 8 (August 1, 2000): 4441–51. http://dx.doi.org/10.1128/iai.68.8.4441-4451.2000.
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ABSTRACT Proteins belonging to the LraI (for “lipoprotein receptor antigen”) family function as adhesins in several streptococci, as a virulence factor for endocarditis in at least one of these species, and potentially as metal transporters in many bacteria. We have identified and characterized the chromosomal locus containing the LraI family gene (designated sloC) from Streptococcus mutans, an agent of dental caries and endocarditis in humans. Northern blot analysis indicated that sloC is cotranscribed with three other genes. As with other LraI operons, the sloA andsloB genes apparently encode components of an ATP-binding cassette transport system. The product of the fourth gene,sloR, has homology to the metal-dependent regulator fromCorynebacterium diphtheriae, DtxR. A potential binding site for SloR was identified upstream from the sloABCR operon and was conserved upstream from LraI operons in several other streptococci. Potential SloR homologs were identified in the unfinished genomic sequences from two of these, S. pneumoniae andS. pyogenes. Mutagenesis of sloC in S. mutans resulted in apparent loss of expression of the entire operon as assessed by Northern blot analysis. The sloCmutant was indistinguishable from its wild-type parent in a gnotobiotic rat model of caries but was significantly less virulent in a rat model of endocarditis. Virulence for endocarditis was restored by correction of the sloC mutation but not by provision of thesloC gene in trans, suggesting that virulence requires the expression of other genes in the sloC operon.
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Cuddapah, Jennifer Locraft, and Shabana Sayed. "Student Learning Objectives (SLOs): Collaboration for Student Success." Global Journal of Educational Studies 5, no. 2 (November 14, 2019): 24. http://dx.doi.org/10.5296/gjes.v5i2.15423.
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A middle school science teacher and a college teacher educator collaborate to explain how the Student Learning Objective (SLO) was embedded into the student teaching internship. After review of the SLO literature, details about the process and benefits of partnering with a mentor teacher in order to learn about the SLO implementation cycle are shared. Implications for future practice are offered.
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Li, Catherine F., and Jeff M. Milunsky. "Smith–Lemli–Opitz Syndrome (SLOS) and the Fetus." Journal of Fetal Medicine 3, no. 2 (May 20, 2016): 51–53. http://dx.doi.org/10.1007/s40556-016-0089-8.
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Zhou, Yu, Qiong-Yao Tang, Xiao-Ming Xia, and Christopher J. Lingle. "Glycine311, a determinant of paxilline block in BK channels: a novel bend in the BK S6 helix." Journal of General Physiology 135, no. 5 (April 26, 2010): 481–94. http://dx.doi.org/10.1085/jgp.201010403.
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The tremorogenic fungal metabolite, paxilline, is widely used as a potent and relatively specific blocker of Ca2+- and voltage-activated Slo1 (or BK) K+ channels. The pH-regulated Slo3 K+ channel, a Slo1 homologue, is resistant to blockade by paxilline. Taking advantage of the marked differences in paxilline sensitivity and the homology between subunits, we have examined the paxilline sensitivity of a set of chimeric Slo1/Slo3 subunits. Paxilline sensitivity is associated with elements of the S5–P loop–S6 module of the Slo1 channel. Replacement of the Slo1 S5 segment or the second half of the P loop results in modest changes in paxilline sensitivity. Replacing the Slo1 S6 segment with the Slo3 sequence abolishes paxilline sensitivity. An increase in paxilline affinity and changes in block kinetics also result from replacing the first part of the Slo1 P loop, the so-called turret, with Slo3 sequence. The Slo1 and Slo3 S6 segments differ at 10 residues. Slo1-G311S was found to markedly reduce paxilline block. In constructs with a Slo3 S6 segment, S300G restored paxilline block, but most effectively when paired with a Slo1 P loop. Other S6 residues differing between Slo1 and Slo3 had little influence on paxilline block. The involvement of Slo1 G311 in paxilline sensitivity suggests that paxilline may occupy a position within the central cavity or access its blocking position through the central cavity. To explain the differences in paxilline sensitivity between Slo1 and Slo3, we propose that the G311/S300 position in Slo1 and Slo3 underlies a structural difference between subunits in the bend of S6, which influences the occupancy by paxilline.
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Talukder, Kaisar A., Abdus S. Mondol, M. Aminul Islam, Zhahirul Islam, Dilip K. Dutta, Bijay K. Khajanchi, Ishrat J. Azmi, et al. "A novel serovar of Shigella dysenteriae from patients with diarrhoea in Bangladesh." Journal of Medical Microbiology 56, no. 5 (May 1, 2007): 654–58. http://dx.doi.org/10.1099/jmm.0.46999-0.
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Every year, around 3 % of isolates from patients with diarrhoea at Dhaka Hospital, ICDDR,B, are identified as Shigella-like organisms (SLOs) based on their activity in biochemical tests. These isolates do not react with any of the current Shigella antisera including all existing and provisional serotypes. Among these SLOs, a unique cluster of seven isolates with an identical plasmid profile was found and these isolates were further characterized by phenotypic and genotypic techniques. All were nonlactose fermenters, with an identical biochemical pattern typical of Shigella dysenteriae. They were classified as invasive since they harboured the 140 MDa invasive plasmid, were able to bind Congo red, produced keratoconjunctivitis in the guinea pig eye, and were positive by PCR for the ipaH gene and Shigella enterotoxin 2 [ShET-2] gene. All isolates were resistant to ampicillin, tetracycline and sulfamethoxazole–trimethoprim but were susceptible to mecillinam, nalidixic acid, ceftriaxone and ciprofloxacin. Six of the isolates were identical in DNA pattern by PFGE with the seventh exhibiting a closely related pattern; both patterns were distinguishable from all other Shigella and Escherichia coli patterns. An antiserum prepared against one of the isolates reacted with all isolates and did not cross-react with other Shigella and E. coli serotype reference strains. It is therefore proposed that these isolates represent a new provisional serovar of S. dysenteriae, type strain KIVI 162.