A Phenomenological Study that Examines the Perseverance of Young Single Mothers Who Have Earned a College Degree

The purpose of this transcendental phenomenological study is to understand perseverance in young single mothers who have earned a college degree. The theory guiding this study is Duckworth’s theory of grit since many students who complete undergraduate degrees experience barriers related to the components of grit. Participants for this study were single mothers who have completed a college degree from an institution of higher learning in central Pennsylvania by the age of thirty. Data for the study were collected utilizing one-on-one interviews, personal timelines, and focus group discussions. Data were analyzed using Moustakas’ data analysis processes, including horizonalization, reduction, and elimination to determine the invariant constituents; clustering and thematizing the invariant constituents; identifying themes; constructing textural descriptions of the experiences; and finally construction textural-structural descriptions of the meanings of the experiences

Sources of Irreproducibility in Machine Learning: A Review

Lately, several benchmark studies have shown that the state of the art in some of the sub-fields of machine learning actually has not progressed despite progress being reported in the literature. The lack of progress is partly caused by the irreproducibility of many model comparison studies. Model comparison studies are conducted that do not control for many known sources of irreproducibility. This leads to results that cannot be verified by third parties. Our objective is to provide an overview of the sources of irreproducibility that are reported in the literature. We review the literature to provide an overview and a taxonomy in addition to a discussion on the identified sources of irreproducibility. Finally, we identify three lines of further inquiry

DEVELOPMENT, VALIDATION, AND APPLICATIONS OF THE PEPSAVI-MS PIPELINE FOR NATURAL PRODUCT BIOACTIVE PEPTIDE DISCOVERY

The recent increase in multidrug-resistant pathogens and associated morbidity/mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. While natural products are a well-studied source of biologically active small molecules, peptidyl factors contributing to their medicinal properties remain largely unexplored. To expedite the search for this exciting class of compounds this dissertation describes the development, validation, and applications of PepSAVI-MS (Statistically-guided bioactive peptides prioritized via mass spectrometry). This highly versatile pipeline employs whole-cell bioactivity screening coupled with mass spectrometry and bioinformatics to identify bioactive peptides from complex biological extracts (Chapter 2). The development and validation of PepSAVI-MS was originally described using a botanical source through the successful detection and identification of a known antimicrobial peptide, cycloviolacin O2 (cyO2), from Viola odorata (Chapter 3). In addition to pipeline validation, this study widened the known antimicrobial spectrum for V. odorata cyclotides, establishing antibacterial activity of cyO2 against Acinetobacter baumannii, and explored novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast and prostate cancer cell lines. To demonstrate the versatility and wide applicability of PepSAVI-MS, validation studies were performed using fungal (Chapter 4) and bacterial sources (Chapter 5), with optional experimental modifications to highlight pipeline utility. Identification of the virally-encoded antifungal killer toxin KP4 from Ustilago maydis P4 and the bacteriocin Bac-21 from Enterococcus faecalis pPD1 demonstrates proof-of-principle for bioactive peptide discovery from bacterial and fungal secretomes. Using the validated pipeline, a variety of natural product sources are probed to prioritize highly active species for downstream analysis. The plant species Amaranthus tricolor is presented as an example of novel antimicrobial activity identified with PepSAVI-MS (Chapter 6). As demonstrated herein, the developed pipeline is powerful and highly versatile; PepSAVI-MS can incorporate material from a variety of natural product sources and is able to accommodate any developed bioactivity screen. The flexible nature of this pipeline presents a valuable tool for diverse natural product exploration, and has the potential to lead to the discovery of a wealth of bioactive peptides.Doctor of Philosoph

A statistical approach to optimizing paper spray mass spectrometry parameters

Rationale Paper spray mass spectrometry (PS‐MS) was used to analyze and quantify ampicillin, a hydrophilic compound and frequently utilized antibiotic. Hydrophilic molecules are difficult to analyze via PS‐MS due to their strong binding affinity to paper substrates and low ionization efficiency, among other reasons. Methods Solvent and paper parameters were optimized to increase the extraction of ampicillin from the paper substrate. After optimizing these key parameters, a Resolution IV 1/16 fractional factorial design with two center points was employed to screen eight different design parameters simultaneously. Results Pore size, sample volume, and solvent volume were the most significant factors affecting average peak area under the curve (AUC) and the signal‐to‐blank (S/B) ratio for the 1 μg/mL ampicillin calibrant. After optimizing the key parameters, a linear calibration curve with a range of 0.2 μg/mL to 100 μg/mL was generated (R2 = 0.98) and the limit of detection (LOD) and lower limit of quantification (LLOQ) were calculated to be 0.07 μg/mL and 0.25 μg/mL, respectively. Conclusions The statistical optimization procedure undertaken here increased the mass spectral signal intensity by more than a factor of 40. This statistical method of screening followed by optimization experiments proved faster and more efficient, and produced more drastic improvements than typical one‐factor‐at‐a‐time experiments

Haplotype Mapping of a Diploid Non-Meiotic Organism Using Existing and Induced Aneuploidies

Haplotype maps (HapMaps) reveal underlying sequence variation and facilitate the study of recombination and genetic diversity. In general, HapMaps are produced by analysis of Single-Nucleotide Polymorphism (SNP) segregation in large numbers of meiotic progeny. Candida albicans, the most common human fungal pathogen, is an obligate diploid that does not appear to undergo meiosis. Thus, standard methods for haplotype mapping cannot be used. We exploited naturally occurring aneuploid strains to determine the haplotypes of the eight chromosome pairs in the C. albicans laboratory strain SC5314 and in a clinical isolate. Comparison of the maps revealed that the clinical strain had undergone a significant amount of genome rearrangement, consisting primarily of crossover or gene conversion recombination events. SNP map haplotyping revealed that insertion and activation of the UAU1 cassette in essential and non-essential genes can result in whole chromosome aneuploidy. UAU1 is often used to construct homozygous deletions of targeted genes in C. albicans; the exact mechanism (trisomy followed by chromosome loss versus gene conversion) has not been determined. UAU1 insertion into the essential ORC1 gene resulted in a large proportion of trisomic strains, while gene conversion events predominated when UAU1 was inserted into the non-essential LRO1 gene. Therefore, induced aneuploidies can be used to generate HapMaps, which are essential for analyzing genome alterations and mitotic recombination events in this clonal organism

Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441.

International audienceBackground: During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles (AuNPs), which differed in size and purification grade (presence or absence of sodium citrate residues on the particle surface) in vitro, in the human alveolar type-II (ATII)-like cell lines A549 and NCIH441