Advanced genome-wide screening in human genomic disorders

UBL - phd migration 201

Clemson University’s Teacher Learning Progression Program: Personalized Advanced Credentials for Teachers

This chapter provides an overview of Clemson University\u27s Teacher Learning Progression program, which offers participating middle school science, technology, engineering, and/or mathematics (STEM) teachers with personalized advanced credentials. In contrast to typical professional development (PD) approaches, this program identifies individualized pathways for PD based on teachers\u27 unique interests and needs and offers PD options through the use of a “recommender system”—a system providing context-specific recommendations to guide teachers toward the identification of preferred PD pathways and content. In this chapter, the authors introduce the program and highlight (1) the data collection and instrumentation needed to make personalized PD recommendations, (2) the recommender system, and (3) the personalized advanced credential options. The authors also discuss lessons learned through initial stages of project implementation and consider future directions for the use of recommender systems to support teacher PD, considering both research and applied implications and settings

Novel mesoporous carbon-silica composites from vinasse for the removal of dyes from aqueous silk dyeing wastes

Novel mesoporous carbon-silica composites were prepared from vinasse, a by-product from ethanol production, as the carbon source, and sodium silicate (Na2SiO3) and potassium silicate (K2SiO3) as low-cost silica source alternatives to tetraethyl orthosilicate (TEOS). The composites were characterized for their surface area and porous properties using nitrogen adsorption-desorption porosimetry. The composites possessed a high mesopore volume (45-77%) with moderate specific surface areas (343-656 m2/g) and pore size of 3.12-5.58 nm. The adsorption behaviour of carbon-silica composites for the removal of four silk dyes (Green 41, Blue 32, Dark red 34 and Dark gold brown 35) from aqueous solution was investigated and compared with a commercial activated carbon. The effects of adsorption time, dye concentration, pH and temperature were analyzed. The dye adsorption kinetics of all four dyes followed the pseudo-second order kinetic model, suggesting chemisorption as the dominant mechanism. Moreover, the intraparticle diffusion model showed that both internal diffusion and external diffusion were rate-limiting. The maximum adsorption capacities for all dyes were found at pH ~ 2. The equilibrium data for silk dyes adsorption were best described by the Langmuir equation, thus indicating monolayer adsorption. Thermodynamic parameters indicated that the dye adsorption was an endothermic process (ΔH > 0). The negative values of free energy (ΔG) confirmed that dye adsorption was spontaneous at the investigated temperatures (303-323 K). For all dyes, the maximum adsorption capacities of carbon-silica composites were comparable to the commercial activated carbon. The combination of vinasse with low-cost silica sources is a promising approach to produce inexpensive carbon-silica composites for application as adsorbents for dye removal from aqueous waste solutions generated during silk manufacture and dyeing

What am I not seeing? An Interactive Approach to Social Content Discovery in Microblogs

In this paper, we focus on the informational and user experience benefits of user-driven topic exploration in microblog communities, such as Twitter, in an inspectable, controllable and personalized manner. To this end, we introduce ``HopTopics'' -- a novel interactive tool for exploring content that is popular just beyond a user's typical information horizon in a microblog, as defined by the network of individuals that they are connected to. We present results of a user study (N=122) to evaluate HopTopics with varying complexity against a typical microblog feed in both personalized and non-personalized conditions. Results show that the HopTopics system, leveraging content from both the direct and extended network of a user, succeeds in giving users a better sense of control and transparency. Moreover, participants had a poor mental model for the degree of novel content discovered when presented with non-personalized data in the Inspectable interface

Evaluation of the antigen-experienced B-cell receptor repertoire in healthy children and adults

Upon antigen recognition via their B cell receptor (BR), B cells migrate to the germinal center where they undergo somatic hypermutation (SHM) to increase their affinity for the antigen, and class switch recombination (CSR) to change the effector function of the secreted antibodies. These steps are essential to create an antigen-experienced BR repertoire that efficiently protects the body against pathogens. At the same time, the BR repertoire should be selected to protect against responses to self-antigen or harmless antigens. Insights into the processes of SHM, selection, and CSR can be obtained by studying the antigen-experienced BR repertoire. Currently, a large reference data set of healthy children and adults, which ranges from neonates to the elderly, is not available. In this study, we analyzed the antigen-experienced repertoire of 38 healthy donors (HD), ranging from cord blood to 74 years old, by sequencing IGA and IGG transcripts using next generation sequencing. This resulted in a large, freely available reference data set containing 412,890 IGA and IGG transcripts. We used this data set to study mutation levels, SHM patterns, antigenic selection, and CSR from birth to elderly HD. Only small differences were observed in SHM patterns, while the mutation levels increase in early childhood and stabilize at 6 years of age at around 7%. Furthermore, comparison of the antigen-experienced repertoire with sequences from the naive immune repertoire showed that features associated with autoimmunity such as long CDR3 length and IGHV4-34 usage are reduced in the antigen-experienced repertoire. Moreover, IGA2 and IGG2 usage was increased in HD in higher age categories, while IGG1 usage was decreased. In addition, we studied clonal relationship in the different samples. Clonally related sequences were found with different subclasses. Interestingly, we found transcripts with the same CDR1-CDR3 sequence, but different subclasses. Together, these data suggest that a single antigen can provoke a B-cell response with BR of different subclasses and that, during the course of an immune response, some B cells change their isotype without acquiring additional SHM or can directly switch to different isotypes

When transcriptome meets metabolome: fast cellular responses of yeast to sudden relief of glucose limitation

Within the first 5 min after a sudden relief from glucose limitation, Saccharomyces cerevisiae exhibited fast changes of intracellular metabolite levels and a major transcriptional reprogramming. Integration of transcriptome and metabolome data revealed tight relationships between the changes at these two levels. Transcriptome as well as metabolite changes reflected a major investment in two processes: adaptation from fully respiratory to respiro-fermentative metabolism and preparation for growth acceleration. At the metabolite level, a severe drop of the AXP pools directly after glucose addition was not accompanied by any of the other three NXP. To counterbalance this loss, purine biosynthesis and salvage pathways were transcriptionally upregulated in a concerted manner, reflecting a sudden increase of the purine demand. The short-term dynamics of the transcriptome revealed a remarkably fast decrease in the average half-life of downregulated genes. This acceleration of mRNA decay can be interpreted both as an additional nucleotide salvage pathway and an additional level of glucose-induced regulation of gene expression

Second tier testing to reduce the number of non-actionable secondary findings and false-positive referrals in newborn screening for severe combined immunodeficiency

Purpose Newborn screening (NBS) for severe combined immunodeficiency (SCID) is based on the detection of T-cell receptor excision circles (TRECs). TRECs are a sensitive biomarker for T-cell lymphopenia, but not specific for SCID. This creates a palette of secondary findings associated with low T-cells that require follow-up and treatment or are non-actionable. The high rate of (non-actionable) secondary findings and false-positive referrals raises questions about the harm-benefit-ratio of SCID screening, as referrals are associated with high emotional impact and anxiety for parents. Methods An alternative quantitative TREC PCR with different primers was performed on NBS cards of referred newborns (N = 56) and epigenetic immune cell counting was used as for relative quantification of CD3 + T-cells (N = 59). Retrospective data was used to determine the reduction in referrals with a lower TREC cutoff value or an adjusted screening algorithm. Results When analyzed with a second PCR with different primers, 45% of the referrals (25/56) had TREC levels above cutoff, including four false-positive cases in which two SNPs were identified. With epigenetic qPCR, 41% (24/59) of the referrals were within the range of the relative CD3 + T-cell counts of the healthy controls. Lowering the TREC cutoff value or adjusting the screening algorithm led to lower referral rates but did not prevent all false-positive referrals. Conclusions Second tier tests and adjustments of cutoff values or screening algorithms all have the potential to reduce the number of non-actionable secondary findings in NBS for SCID, although second tier tests are more effective in preventing false-positive referrals.Transplantation and immunomodulatio

Immunodeficiency in Bloom’s Syndrome

Bloom’s syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene. This gene codes for BLM protein, which is a helicase involved in DNA repair. DNA repair is especially important for the development and maturation of the T and B cells. Since BLM is involved in DNA repair, we aimed to study if BLM deficiency affects T and B cell development and especially somatic hypermutation (SHM) and class switch recombination (CSR) processes. Clinical data of six BS patients was collected, and immunoglobulin serum levels were measured at different time points. In addition, we performed immune phenotyping of the B and T cells and analyzed the SHM and CSR in detail by analyzing IGHA and IGHG transcripts using next-generation sequencing. The serum immunoglobulin levels were relatively low, and patients had an increased number of infections. The absolute number of T, B, and NK cells were low but still in the normal range. Remarkably, all BS patients studied had a high percentage (20–80%) of CD4+ and CD8+ effector memory T cells. The process of SHM seems normal; however, the Ig subclass distribution was not normal, since the BS patients had more IGHG1 and IGHG3 transcripts. In conclusion, BS patients have low number of lymphocytes, but the immunodeficiency seems relatively mild since they have no severe or opportunistic infections. Most changes in the B cell development were seen in the CSR process; however, further studies are necessary to elucidate the exact role of BLM in CSR