Early-stage social ventures : resource acquisition, CEO selection, and impact investors

Field of study: Business administration.Dr. Karen A. Schnatterly, Dissertation Advisor.Includes vita."July 2018."In this dissertation, I explore early-stage social ventures' resource acquisition, the first CEO selection, as well as how funding foundations supporting early-stage social ventures overcome challenges emerge from the economic crisis. Social ventures are organizations established by social entrepreneurs who seek to create social impact by providing systematic and sustainable solutions. They pursue the integration of social mission and economic goal in organizations' core, thus are distinguished from both commercial organizations and nonprofits. Successful acquisition of seed capital and the first CEO selection are crucial milestones for social ventures to survive and flourish. The proposed model in Chapter 2 suggested factors of social ventures that affect impact investor's eventual investment decision. It explicates how characteristics of a core founder, a founding team, and a social venture relate to each other and contribute to the increasing possibility of seed capital acquisition. Chapter 3 of this dissertation examines the first CEO selection of social venture. I empirically tested hypotheses using a dataset of 261 social entrepreneurs from 108 social ventures and found that previous working experience in social mission-oriented organizations is crucial for being assigned as the first CEO. Additionally, previous working experience in commercial firms contributes to only female social entrepreneurs' possibility of becoming the first CEO. In Chapter 4, I shift the focus to impact investors and explore the survival strategy of a funding foundation, Echoing Green, in response to financial challenges during the economic downturn in 2008.Includes bibliographical references (pages 104-116)

AccessLens: Auto-detecting Inaccessibility of Everyday Objects

In our increasingly diverse society, everyday physical interfaces often present barriers, impacting individuals across various contexts. This oversight, from small cabinet knobs to identical wall switches that can pose different contextual challenges, highlights an imperative need for solutions. Leveraging low-cost 3D-printed augmentations such as knob magnifiers and tactile labels seems promising, yet the process of discovering unrecognized barriers remains challenging because disability is context-dependent. We introduce AccessLens, an end-to-end system designed to identify inaccessible interfaces in daily objects, and recommend 3D-printable augmentations for accessibility enhancement. Our approach involves training a detector using the novel AccessDB dataset designed to automatically recognize 21 distinct Inaccessibility Classes (e.g., bar-small and round-rotate) within 6 common object categories (e.g., handle and knob). AccessMeta serves as a robust way to build a comprehensive dictionary linking these accessibility classes to open-source 3D augmentation designs. Experiments demonstrate our detector's performance in detecting inaccessible objects.Comment: CHI202

HB-EGF Improves the Hair Regenerative Potential of Adipose-Derived Stem Cells via ROS Generation and Hck Phosphorylation

Although adipose-derived stem cells (ASCs) have hair regenerative potential, their hair inductive capabilities are limited. The mitogenic and hair inductive effects of heparin binding-epidermal growth factor-like growth factor (HB-EGF) on ASCs were investigated in this study and the underlying mechanism of stimulation was examined. Cell growth, migration, and self-renewal assays, as well as quantitative polymerase chain reactions and immunostaining, were carried out. Telogen-to-anagen transition and organ culture using vibrissa follicles were also conducted. HB-EGF significantly increased ASC motility, including cell proliferation, migration, and self-renewal activity. The preconditioning of ASCs with HB-EGF induced telogen-to-anagen transition more rapidly in vivo, and injected PKH26-ASCs survived for longer periods of time. Conditioned medium obtained from HB-EGF-treated ASCs promoted hair growth in vivo, upregulating growth factors. In particular, thrombopoietin (THPO) also induced hair growth in vivo, stimulating dermal papilla cells (DPCs). Reactive oxygen species (ROS) appeared to play a key role in ASC stimulation as the inhibition of ROS generation and NOX4 knockout attenuated ASC stimulation and THPO upregulation by HB-EGF. In addition, the Hck phosphorylation pathway mediated the stimulation of ASCs by HB-EGF. In summary, HB-EGF increased the motility and paracrine effects of ASCs releasing THPO growth factor and THPO promoted hair growth-stimulating DPCs. ROS generation and Hck phosphorylation are key factors in HB-EGF-induced ASC stimulation. Therefore, combination therapy involving HB-EGF and ASCs may provide a novel solution for hair-loss treatment

Synthesis and Application of N-methylphthalimidylazo Disperse Dyes to Cellulose Diacetate for High Wash Fastness

Cellulose diacetate fibers were prepared from cellulosic biomass with high α-cellulose contents such as purified cotton linters and wood pulps. Cellulose diacetate fibers are sensitive to alkaline solution, which causes hydrolysis of the acetate ester to hydroxyl groups, especially at high temperatures. Thus, the low alkali-resistance of cellulose acetate fibers makes it difficult to achieve high wash fastness by restricting the application of intense after-treatment, such as reduction clearing. A series of N-methylphthalimide-based high-washable azo disperse dyes were synthesized and their dyeing and fastness properties on cellulose diacetate fabrics were investigated. From the overall results obtained in this study, N-methylphthalimidylazo disperse dyes are expected to be a desirable alternative to high value-added dyes that can be used for high color fastness dyeing of cellulose diacetate with a minimal discharge of wastewater during washing process

Salinomycin decreases the CD44⁺/CD24^- stem-like population during anchorage-independent growth and inhibits mammosphere formation.

<p>(A) The CD44⁺/CD24^- stem-like population in several breast cancer cell lines [luminal-type (MCF7 and T47D), HER2-amplified (BT474, MDA-MB-453, and SKBR3) and TNBC (MDA-MB-231)] was evaluated by flow cytometry. (B) Effect of salinomycin (2 μM, 48 h) on CD44⁺/CD24^- levels in anchorage-dependent and -independent conditions. The graph represents the percentage of CD44⁺/CD24^- cells (right panel). Data are expressed as mean ± SEM (n = 3, independent experiments) and were analyzed by two-way ANOVA followed by Bonferroni’s <i>post hoc</i> test (++ <i>p</i><0.01, versus anchorage-independent DMSO control; NS, not significant). (C) MDA-MB-231 and 4T1 mammospheres were cultured for 5 days in serum-free suspension conditions in the presence or absence of salinomycin (2 μM). Graphs represents the number (per 10⁴ cells) and volumes (mm³) of mammospheres (bottom panel, Student’s t-test, ** <i>p</i><0.01).</p

Salinomycin induces anoikis-sensitivity.

<p>(A) After exposure to salinomycin (0.5–2 μM) or DMSO for 24–48 h, the sub-G1 population was examined by flow cytometry. The percentage of cells in the sub-G1 fraction (red arrow) is depicted in the plot. (B-D) MDA-MB-231 and (E-F) 4T1 cells were grown in plates that were either uncoated or coated with poly-HEMA (2-hydroxyethyl methacrylate, 10 mg/ml) for 24 h and then treated with salinomycin (0.5–2 μM) or DMSO. (B) Effect of salinomycin on the sub-G1 fraction in anchorage-dependent and -independent conditions. The graph represents the percentage of cells in sub-G1 (++ <i>p</i><0.01 and # <i>p</i><0.05). (C) Effect of salinomycin on levels of apoptosis-related factors in MDA-MB-231 anchorage-dependent and -independent cells. Actin was used as a loading control. Quantitative graphs of cleaved caspase-3, cleaved caspase-8, and survivin signal intensity are shown (right panel, + <i>p</i><0.05 and ## <i>p</i><0.01). (D) Salinomycin (2 μM, 48 h) significantly increased the number of early and late apoptotic cells in anchorage-independent growth. The graph represents the percentage of annexin V-positive cells (bottom panel, + <i>p</i><0.05). (E) Effect of salinomycin on levels of apoptosis-related factors in 4T1 anchorage-dependent and -independent cells. Quantification of cleaved caspase-3 and survivin are shown (right panel, +++ <i>p</i><0.001 and ### <i>p</i><0.001). (F) Early and late apoptotic cells were increased following salinomycin treatment (0.5 μM, 48 h) in 4T1 anchorage-independent growth. The percentage of annexin V-positive cells are shown in the graph (bottom panel, + <i>p</i><0.05). The results are expressed as mean ± SEM and were analyzed by two-way ANOVA followed by Bonferroni’s <i>post hoc</i> test (+ <i>p</i><0.05, ++ <i>p</i><0.01, and +++ <i>p</i><0.001, versus anchorage-independent DMSO control; # <i>p</i><0.05, ## <i>p</i><0.01, and ### <i>p</i><0.001, versus each concentration; NS, not significant). All experiments were independently performed at least three times (n = 3).</p

Salinomycin suppresses cell viability.

<p>TNBC cell lines [(A) MDA-MB-231 and (B) 4T1 cells] were treated with salinomycin (0.5–10 μM) or vehicle (DMSO) for the indicated durations. Viable cells were evaluated by MTS assay. Results are expressed as mean ± SEM and were analyzed by two-way ANOVA followed by Bonferroni’s <i>post hoc</i> test (*<i>p</i><0.05, ** <i>p</i><0.01 and *** <i>p</i><0.001, versus DMSO control). The experiment was independently performed three times (n = 3). Sal, salinomycin.</p

Altered secretome by diesel exhaust particles and lipopolysaccharide in primary human nasal epithelium

© 2022 The AuthorsBackground: Airway epithelial cells can actively participate in the defense against environmental pathogens to elicit local or systemic inflammation. Diesel exhaust particles (DEP), a main component of urban air pollution with particulate matter, are associated with the occurrence of acute and chronic upper airway inflammatory diseases. Objectives: We sought to investigate the effect of DEP alone or in combination with lipopolysaccharide on the secretome in the primary human nasal epithelium (PHNE) and to find potential biomarkers to relate DEP exposure to upper airway inflammatory diseases. Methods: PHNE was cultured at an air–liquid interface to create a differentiated in vivo–like model. Secreted proteins (secretome) on the bottom media of the PHNE were analyzed by mass spectrometry–based label-free quantitative proteomics and ELISA. Results: Considerably more differentially expressed secreted proteins were identified in response to DEP plus lipopolysaccharide than to DEP alone. Some canonical pathways related to inflammation and cancer such as the p53, β-catenin, and extracellular signal-regulated kinase 1/2 pathways were involved. Among differentially expressed secreted proteins, leukemia inhibitory factor was also detected at a high level in the middle ear effusions of otitis media patients, and the leukemia inhibitory factor level was significantly correlated with daily mean mass concentrations of atmospheric particulate matter averaged over 8 days before sample collection. Conclusions: Apical stimulation with DEP and lipopolysaccharide can significantly alter the basal secretome in PHNE, and this alteration can be reflected by surrounding inflammation with effusion of fluids in vivo such as middle ear effusions in otitis media patients.N

Combination effect of salinomycin and STAT3 inhibitors on apoptosis, migration, and CD44⁺/CD24^- stem-like population.

<p>(A) Cells were treated with salinomycin (2 μM, 48 h) and/or S3I-201 (50 μM) or LLL12 (1 μM) and annexin V/PI analysis was performed. Quantitative graph of annexin V-positive population is shown (bottom panel, *** <i>p</i><0.001 and ### <i>p</i><0.001). (B) Effect of combined treatment with salinomycin and S3I-201 on protein expression of STAT3, phospho-STAT3, cyclin D1, and apoptosis-related factors. (C) Cells were co-treated with salinomycin (2 μM) and S3I-201 (50 μM) or LLL12 (1 μM) and the relative wound density was assessed over 24 h. Quantitative graph of relative migration is presented (** <i>p</i><0.01 and ## <i>p</i><0.01). (D) Effect of salinomycin (2 μM, 48 h) combined with S3I-201 (50 μM) or LLL12 (1 μM) on the CD44⁺/CD24^- stem-like population. The graph represents the percentage of CD44⁺/CD24^- cells (bottom panel, * <i>p</i><0.05 and ## <i>p</i><0.01). The results were expressed as mean ± SEM and analyzed by one-way ANOVA followed by Bonferroni’s <i>post hoc</i> test (* <i>p</i><0.05, ** <i>p</i><0.01, and *** <i>p</i><0.001, versus DMSO control; ## <i>p</i><0.01 and ### <i>p</i><0.001, versus salinomycin only). All experiments were independently performed at least three times (n = 3).</p