Metagenomic sequencing, microbiome reconstruction, and analysis of ancient North and Central American dental calculus

Analyses of human oral microbiomes reveal substantial amounts of information about health, diet, and diseases of individuals and their communities within the archaeological record. In order to examine bacterial genomes from the past, specific archaeological samples that contain remnants of the microbial communities in question must be utilized. Recent developments in high-throughput, next-generation DNA sequencing have enabled the characterization of entire oral microbiomes and genomes from the remains of the bacteria trapped in calcified dental plaque. This project analyzed samples of ancient human dental calculus from North and Central America, which were examined for the changes within the oral microbiome in relation to the adoption of agriculture. Additionally, the conditional presence of pathogens associated with an increasingly agricultural and carbohydrate-rich diet was examined. The overarching goal was to examine and determine the level of microbial shifts within the past oral microbiomes of North and Central America, and by virtue of using the associated archaeological reports and analyses, place the data into the proper context. Three distinct sets of dental calculus were used for this Dissertation; The first is from Indigenous samples (N=56), spanning from the Archaic to the Mississippian, recovered from excavations in the Guntersville Basin in Northern Alabama. The second set is from a Late-Terminal Classic Maya city center and satellite village in the Upper Belize Valley (N=11). The final sample set comes from an archaeologically recovered early 20th century Cemetery near Jackson Mississippi (N=12). After individual analyses, they are all examined along a temporal axis to examine the effect of agriculture on the human oral microbiome. The findings from this study have shown that oral microbiomes of the Americas were affected by the introduction of agriculture, but remained biologically diverse. Because various subsistence strategies can shape and affect the oral microbiome, the composition is seen to change over time. Our understanding of the evolution of oral microbiomes throughout human history is more complex than previously thought; there is no global trend for the oral microbiome, but is highly location dependent

The Reconstruction and Analysis of Oral Microbiome Composition Using Dental Calculus from the Mississippi State Asylum (1855-1935), Jackson, Ms

The human oral microbiome is the total amount of microbial biodiversity present in the oral cavity and, given its relevance to human health and disease, has recently become a foci for study. By analyzing dental calculus, and sequencing the bacterial DNA, it is possible to reconstruct and examine the oral microbiomes of past individuals. In this study, dental calculus was sampled from (N=4) skeletons recovered from the cemetery of the mid 19th- 20th, century Mississippi State Asylum in Jackson, MS. Bacterial DNA isolation and shotgun sequencing were successful, with 16S analyses yielding an average of 96 identified species. All samples were significantly different from each other at all taxonomic levels (p \u3c0.0001). Targeted examinations for opportunistically pathogenic oral bacteria were performed, but no detectable bacterial DNA was found in the samples. This study is the first to reconstruct the oral microbiomes of a subsample of an historic institutionalized population

The Reconstruction and Analysis of Oral Microbiome Composition Using Dental Calculus from the Mississippi State Asylum (1855-1935), Jackson, Ms

The human oral microbiome is the total amount of microbial biodiversity present in the oral cavity and, given its relevance to human health and disease, has recently become a foci for study. By analyzing dental calculus, and sequencing the bacterial DNA, it is possible to reconstruct and examine the oral microbiomes of past individuals. In this study, dental calculus was sampled from (N=4) skeletons recovered from the cemetery of the mid 19th- 20th, century Mississippi State Asylum in Jackson, MS. Bacterial DNA isolation and shotgun sequencing were successful, with 16S analyses yielding an average of 96 identified species. All samples were significantly different from each other at all taxonomic levels (p \u3c0.0001). Targeted examinations for opportunistically pathogenic oral bacteria were performed, but no detectable bacterial DNA was found in the samples. This study is the first to reconstruct the oral microbiomes of a subsample of an historic institutionalized population

LanSER: Language-Model Supported Speech Emotion Recognition

Speech emotion recognition (SER) models typically rely on costly human-labeled data for training, making scaling methods to large speech datasets and nuanced emotion taxonomies difficult. We present LanSER, a method that enables the use of unlabeled data by inferring weak emotion labels via pre-trained large language models through weakly-supervised learning. For inferring weak labels constrained to a taxonomy, we use a textual entailment approach that selects an emotion label with the highest entailment score for a speech transcript extracted via automatic speech recognition. Our experimental results show that models pre-trained on large datasets with this weak supervision outperform other baseline models on standard SER datasets when fine-tuned, and show improved label efficiency. Despite being pre-trained on labels derived only from text, we show that the resulting representations appear to model the prosodic content of speech.Comment: Presented at INTERSPEECH 202

Know Thy Learner: User Characteristics Underlying Effective Videogame-Based Training

Some proponents of training games argue that younger adults (Soldiers) are part of the "digital"or "twitch" generation, having grown up uing computers and playing videogames (e.g.,Prensky,2001). The Entertainment Software Association (ESA) reports that 69%of American heads of households play computer and/or videogames. "65% of college students reported being regular or occasional game players" (Jones, 2003)

Sequential administration of temozolomide and fotemustine: Depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours

Background: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitro-soureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloro-ethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. Patients and methods: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. Results: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. Conclusions: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therap

10 simple rules to create a serious game, illustrated with examples from structural biology

Serious scientific games are games whose purpose is not only fun. In the field of science, the serious goals include crucial activities for scientists: outreach, teaching and research. The number of serious games is increasing rapidly, in particular citizen science games, games that allow people to produce and/or analyze scientific data. Interestingly, it is possible to build a set of rules providing a guideline to create or improve serious games. We present arguments gathered from our own experience ( Phylo , DocMolecules , HiRE-RNA contest and Pangu) as well as examples from the growing literature on scientific serious games

Climbing Bloom’s taxonomy pyramid: Lessons from a graduate histology course

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138235/1/ase1685_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138235/2/ase1685.pd

Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours

BACKGROUND: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. PATIENTS AND METHODS: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. RESULTS: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. CONCLUSIONS: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy