March 2017

Dag, Ali, Oztekin, A., Yucel, A., Bulur, S., & Megahed, F. M. (2017). Predicting heart transplantation outcomes through data analytics. Decision Support Systems, 94, 42-52.

Predicting the survival of heart transplant patients is an important, yet challenging problem since it plays a crucial role in understanding the matching procedure between a donor and a recipient. Data mining models can be used to effectively analyze and extract novel information from large/complex transplantation datasets. The objective of this study is to predict the 1-, 5-, and 9-year patient’s graft survival following a heart transplant surgery via the deployment of analytical models that are based on four powerful classification algorithms (i.e. decision trees, artificial neural networks, support vector machines, and logistic regression). Since the datasets used in this study has a much larger number of survival cases than deaths for 1- and 5-year survival analysis and vice versa for 9-year survival analysis, random under sampling (RUS) and synthetic minority over-sampling (SMOTE) are employed to overcome the data-imbalance problems. The results indicate that logistic regression combined with SMOTE achieves the best classification for the 1-, 5-, and 9-year outcome prediction, with area-under-the-curve (AUC) values of 0.624, 0.676, and 0.838, respectively. By applying sensitivity analysis to the data analytical models, the most important predictors and their associated contribution for the 1-, 5-, and 9-year graft survival of heart transplant patients are identified. By doing so, variables, whose importance changes over time, are differentiated. Not only this proposed hybrid approach gives superior results over the literature but also the models and identification of the variables present important retrospective findings, which can be the basis for a prospective medical study. (C) 2016 Elsevier B.V. All rights reserved.

Beacom School of Business.

 

Freeling, Jessica L., & Rezvani, Khosrow. (2016). Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging. Molecular Therapy-Methods & Clinical Development, 3, 11.

The relatively low success rates of current colorectal cancer (CRC) therapies have led investigators to search for more specific treatments. Vertebrate models of colorectal cancer are essential tools for the verification of new therapeutic avenues such as gene therapy. The evaluation of colorectal cancer in mouse models has been limited due to the lack of an accurate quantitative and longitudinal noninvasive method. This work introduces a method of three-dimensional micro-ultrasound reconstruction and – microbubble administration for the comprehensive and longitudinal evaluation of CRC progression. This approach enabled quantification of both tumor volume and relative vascularity using a well-established inducible murine model of colon carcinogenesis. This inducible model recapitulated the adenocarcinoma sequence that occurs in human CRC allowing systematic in situ evaluation of the ultrasound technique. The administration of intravenous microbubbles facilitated enhancement of colon vascular contrast and quantification of relative vascularity of the mid and distal colon of the mouse in three dimensions. In addition, two-dimensional imaging in the sagittal orientation of the colon using Non-Linear Contrast Mode enabled calculation of relative blood volume and perfusion as the microbubbles entered the colon microvasculature. Quantitative results provided by the outlined protocol represent a noninvasive tool that can more accurately define CRC development and progression. This ultrasound technique will allow the practical and economical longitudinal study of murine CRC in both basic and preclinical studies.

Basic Biomedical Sciences, Vermillion Campus.

 

Grassmeyer, Justin, Mukherjee, Malini, …., Zhao, Haotian,Fogarty, Eric, & Surendran, Kameswaran. (2017). Elf5 is a principal cell lineage specific transcription factor in the kidney that contributes to Aqp2 and Avpr2 gene expression. Developmental Biology, 424(1), 77-89.

The mammalian kidney collecting ducts are critical for water, electrolyte and acid-base homeostasis and develop as a branched network of tubular structures composed of principal cells intermingled with intercalated cells. The intermingled nature of the different collecting duct cell types has made it challenging to identify unique and critical factors that mark and/or regulate the development of the different collecting duct cell lineages. Here we report that the canonical Notch signaling pathway components, RBPJ and Presinilin1 and 2, are involved in patterning the mouse collecting duct cell fates by maintaining a balance between principal cell and intercalated cell fates. The relatively reduced number of principal cells in Notch-signaling-deficient kidneys offered a unique genetic leverage to identify critical principal cell-enriched factors by transcriptional profiling. Elf5 , which codes for an ETS transcription factor, is one such gene that is down-regulated in kidneys with Notch-signaling-deficient collecting ducts. Additionally, Elf5 is among the earliest genes up regulated by ectopic expression of activated Notch1 in the developing collecting ducts. In the kidney, Elf5 is first expressed early within developing collecting ducts and remains on in mature principal cells. Lineage tracing of Elf5 -expressing cells revealed that they are committed to the principal cell lineage by as early as E16.5. Over-expression of ETS Class IIa transcription factors, including Elf5, Elf3 and Ehf, increase the transcriptional activity of the proximal promoters of Aqp2 and Avpr2 in cultured ureteric duct cell lines. Conditional inactivation of Elf5 in the developing collecting ducts results in a small but significant reduction in the expression levels of Aqp2 and Avpr2 genes. We have identified Elf5 as an early maker of the principal cell lineage that contributes to the expression of principal cell specific genes.

Sanford School of Medicine, Sioux Falls Campus.

 

Jacobs, Gerard A., Gray, Brandon L., Erickson, Sara E.,Gonzalez, Elvira D., & Quevillon, Randal P. (2016). Disaster Mental Health and Community-Based Psychological First Aid: Concepts and Education/Training. Journal of Clinical Psychology, 72(12), 1307-1317.

Any community can experience a disaster, and many traumatic events occur without warning. Psychologists can be an important resource assisting in psychological support for individuals and communities, in preparation for and in response to traumatic events. Disaster mental health and the community-based model of psychological first aid are described. The National Preparedness and Response Science Board has recommended that all mental health professionals be trained in disaster mental health, and that first responders, civic officials, emergency managers, and the general public be trained in community-based psychological first aid. Education and training resources in these two fields are described to assist psychologists and others in preparing themselves to assist their communities in difficult times and to help their communities learn to support one another. (C) 2016 Wiley Periodicals, Inc.

Psychology Department.

 

Liao, Y. N., Liu, N. N., Hua, X. L., Cai, J. Y., Xia, X. H., Wang, Xuejun, . . . Liu, J. B. (2017). Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor. Cell Death & Disease, 8, 9.

Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated. In the current study, we have identified ubiquitin-specific protease 14 (USP14) as a novel regulator of AR, inhibiting the degradation of AR via deubiquitinating this oncoprotein in the androgen-responsive prostate cancer cells. We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells. Hence, we conclude that USP14 promotes prostate cancer progression likely through stabilization of AR, suggesting that USP14 could be a promising therapeutic target for prostate cancer.

Basic Biomedical Sciences, Vermillion Campus.

 

Li, Jie, Ma, Wenxia, Yue, Guihua, …., Wang, Xuejun, & Su, Huabo. (2017). Cardiac proteasome functional insufficiency plays a pathogenic role in diabetic cardiomyopathy.Journal of Molecular & Cellular Cardiology, 102, 53-60.

Background Diabetic cardiomyopathy is a major risk factor in diabetic patients but its pathogenesis remains poorly understood. The ubiquitin-proteasome system (UPS) facilitates protein quality control by degrading unnecessary and damaged proteins in eukaryotic cells, and dysfunction of UPS is implicated in various cardiac diseases. However, the overall functional status of the UPS and its pathophysiological role in diabetic cardiomyopathy have not been determined. Methods and results Type I diabetes was induced in wild-type and transgenic mice expressing a UPS functional reporter (GFPdgn) by injections of streptozotocin (STZ). STZ-induced diabetes progressively impaired cardiac UPS function as evidenced by the accumulation of GFPdgn proteins beginning two weeks after diabetes induction, and by a buildup of total and lysine (K) 48-linked polyubiquitinated proteins in the heart. To examine the functional role of the UPS in diabetic cardiomyopathy, cardiac overexpression of PA28α (PA28αOE) was used to enhance proteasome function in diabetic mouse hearts. PA28αOE diabetic mice displayed exhibited restoration of cardiac UPS function, as demonstrated by the diminished accumulation of GFPdgn and polyubiquitinated proteins. Moreover, PA28αOE diabetic mice exhibited reduced myocardial collagen deposition, decreased cardiomyocyte apoptosis, and improved cardiac systolic and diastolic function. Conclusion Impairment of cardiac UPS function is an early event in STZ-induced diabetes. Overexpression of PA28α attenuates diabetes-induced proteotoxic stress and cardiomyopathy, suggesting a potential therapeutic role for enhancement of cardiac proteasome function in this disorder.

Basic Biomedical Sciences, Vermillion Campus.

 

Puckett, Jae A., Horne, Sharon G., Maroney, Meredith R., Herbitter, Cara, & Levitt, Heidi M. (2017). Differences Across Contexts. Psychology of Women Quarterly, 41(1), 8-19.

Minority stressors encountered by lesbian, gay, and bisexual (LGB) women are inherently connected to contextual experiences. Although there is a growing body of research on the benefits of gaining political rights and the costs of their denial, little research has focused on the effects of access to LGB-affirmative resources. In the current study with 1,017 women in same-sex relationships, we created profiles using latent class analysis to characterize the contexts in which participants were raised and the contexts in which they lived at the time of the study. We examined differences in interpersonal relationships, internalized heterosexism (IH), and outness across these profiles. Class 1 (28%) included participants who always lived in affirmative contexts with LGB-supportive resources. Class 2 participants (28%) always lived in more heterosexist contexts with few resources. Class 3 participants (44%) originally lived in more heterosexist contexts with few resources but shifted to more affirmative contexts. Class 3 individuals had greater social support and lower IH than Class 2 participants. Classes 1 and 3 had greater outness than Class 2. This study provides evidence linking IH to the lack of contextual supports. Our data also suggest that the quality of relationships for LGB women may remain strong even in heterosexist contexts. Actions that increase affirming resources will provide avenues for more positive identity development and interpersonal relationships for LGB individuals.

Psychology Department.

 

Quevillon, Randal P., Gray, Brandon L., Erickson, Sara E.,Gonzalez, Elvira D., & Jacobs, Gerard A. (2016). Helping the Helpers: Assisting Staff and Volunteer Workers Before, During, and After Disaster Relief Operations. Journal of Clinical Psychology, 72(12), 1348-1363.

Self-care strategies and system supports employed in preparation for, during, and after disaster relief operations (DROs) are crucial to relief worker well-being and the overall effectiveness of relief efforts. Relief organizations and management must structure DROs in a manner that promotes self-care and workers must implement proper self-care strategies. Proper self-care before, during, and after a DRO can reduce negative reactions to stressful emergency work and promote growth, mastery, and self-efficacy after the experience. Therefore, the purpose of this article is to discuss the importance of organizational supports and self-care strategies in disaster relief settings. This article emphasizes the role of both individual and management participation and commitment to relief worker support and positive experience in DROs and provides suggestions for doing so. These suggestions are derived from the empirical and experiential literature and extensions from the theoretical background, and from our experience as managers in DROs. (C) 2016 Wiley Periodicals, Inc.

Psychology Department.

 

Roh, Soonhee, Burnette, Catherine E., Lee, Kyoung Hag, Lee, Yeon-Shim, & Easton, Scott D. (2016). Risk and protective factors for depressive symptoms among indigenous older adults: Intimate partner violence (IPV) and social support. Journal of Gerontological Social Work, 59(4), 316-331.

Research on depression and intimate partner violence (IPV) experienced by Indigenous older adults is virtually nonexistent. Given the associations between IPV and depression and their disproportionately high rates among Indigenous peoples in a context of historical oppression, the purpose of this inquiry is to examine how IPV and social support are associated with depressive symptoms for Indigenous older adults. We expand the knowledge base on IPV in later life, which primarily focuses on female samples, by including older men. We predicted: (a) IPV will be positively associated with depressive symptoms and (b) levels of social support will be negatively associated with depressive symptoms. Hierarchical regression analyses of data from a sample of Indigenous older adults (N = 233) in the Upper Midwest indicated that physical aggression (but not psychological aggression, sexual coercion, injury, or negotiation) was positively associated with depressive symptoms, whereas social support was negatively associated with depressive symptoms.

School of Health Sciences.

 

Son, Jung-Ho, Tamang, Sem Raj, Fostvedt, Jade, &Hoefelmeyer, James D. (2017). Dehydrodechlorination of Methylene Chloride, Chloroform, and Chlorodiphenylmethane in the Presence of Ga/N Lewis Pairs. Organometallics, 36(2), 474-479.

Transmetalation occurs upon addition of GaCl3 to (quinolin-8-yl)trimethylstannane. The compound dissolves immediately in pyridine, and recrystallization gives dichloropyridinyl(quinolin-8-yl)gallium(III). In chloroform, the compound bis-mu-(quinolin-8-y1)-mu-chloro-dichlorodigallium(III) tetrachloro-gallate could be isolated in small quantities; however, the major product was trichloro(quinolinium-8-yl)gallate(III) zwitterion. The zwitterion also formed upon addition of methylene chloride or chlorodiphenylmethane. We hypothesize that the highly electrophilic digallyl cation abstracts chloride to form a carbocation and that proton transfer from the carbocation to the quinoline nitrogen affords transient carbenes. In particular, diphenyl carbene forms from dehydrodechlorination of chlorodiphenylmethane in toluene/cyclohexene to give a well-defined mixture of products due to cyclopropanation and C-H insertion reactions. Dichloropyridinyl(quinolin-8-yl)gallium(III) undergoes reaction with chloroform only at elevated temperature to yield quinolinium tetrachlorogallate salt as the product. This salt also forms in the reaction of chloroform with GaCl3 and quinoline at elevated temperature. The zwitterion could be converted to quinolinium tetrachlorogallate upon heating, which supports the idea that it was formed initially as an intermediate. Thus, the Ga/N Lewis pairs appear capable of dehydrodechlorination of chloroalkanes.

Chemistry Department.

 

Swanson, David L., King, Marisa O., Culver Iii, William, & Yufeng, Zhang. (2017). Within-Winter Flexibility in Muscle Masses, Myostatin, and Cellular Aerobic Metabolic Intensity in Passerine Birds. Physiological & Biochemical Zoology, 90(2), 210-222.

Metabolic rates of passerine birds are flexible traits that vary both seasonally and among and within winters. Seasonal variation in summit metabolic rates (Msum = maximum thermoregulatory metabolism) in birds is consistently correlated with changes in pectoralis muscle and heart masses and sometimes with variation in cellular aerobicmetabolic intensity, so these traits might also be associated with shorter-term, within-winter variation in metabolic rates. To determine whether these mechanisms are associated with within-winter variation in Msum, we examined the effects of short-term (ST; 0-7 d), medium-term (MT; 14-30 d), and long-term (LT; 30-yr means) temperature variables on pectoralis muscle and heart masses, pectoralis expression of the muscle-growth inhibitor myostatin and its metalloproteinase activators TLL-1 and TLL-2, and pectoralis and heart citrate synthase (CS; an indicator of cellular aerobic metabolic intensity) activities for two temperate-zone resident passerines, house sparrows (Passer domesticus) and dark-eyed juncos (Junco hyemalis). For both species, pectoralis mass residuals were positively correlated with ST temperature variables, suggesting that cold temperatures resulted in increased turnover of pectoralis muscle, but heart mass showed little within-winter variation for either species. Pectoralis mRNA and protein expression of myostatin and the TLLs were only weakly correlated withSTandMTtemperature variables, which is largely consistent with trends in muscle masses for both species. Pectoralis and heart CS activities showed weak and variable trends with ST temperature variables in both species, suggesting only minor effects of temperature variation on cellular aerobic metabolic intensity. Thus, neither muscle or heart masses, regulation by the myostatin system, nor cellular aerobicmetabolic intensity varied consistently with winter temperature, suggesting that other factors regulate within-winter metabolic variation in these birds.

Biology Department.

 

Tjarks, B. Joel, Somani, N., Piliang, M., & Bergfeld, W. F. (2017). A proposed classification for follicular involvement by melanoma. Journal of Cutaneous Pathology, 44(1), 45-52.

Background: Folliculotropism in melanoma is poorly characterized and standard categorization for follicular involvement by melanoma is unavailable. We propose a logical categorization system. Methods: We conducted a search of our archives over a 24-year period for cases mentioning the terms follicle, follicular, folliculotropic, folliculocentric and melanoma. Results: We identified 90 cases of melanoma with involvement of the hair follicle. Distinct patterns were identified. The invasive patterns were primary follicular, folliculotropic and invasive arising from melanoma in situ (MIS) with extensive follicular involvement. Follicular involvement by MIS was either lentiginous, nested or a combination of both. A total of 29 invasive melanomas were identified. Of these 12 had invasive melanoma around the hair follicle, 2 were primary follicular melanomas, 7 showed folliculotropism and 3 were invasive melanomas arising from MIS around the follicle. Seventeen invasive melanomas had follicles only involved by MIS (9 nested, 6 nested and lentiginous and 2 lentiginous). A total of 61 cases of MIS with follicular involvement were identified; of these 33 were lentiginous, 10 nested and 18 both lentiginous and nested. Conclusion: We propose that the three distinct patterns of follicular involvement by invasive melanoma and the three distinct patterns of MIS will be valuable for logically categorizing involvement of the hair follicle by melanoma.

Sanford School of Medicine, Sioux Falls Campus.

 

Wang, X. T., & Gang, H. F. (2017). Glucose-specific signaling effects on delay discounting in intertemporal choice.Physiology & Behavior, 169, 195-201.

We propose that decisions related to resource management (e.g., intertemporal choice between a smaller-and-sooner reward and a larger-and-later reward) are sensitive to and regulated by fluctuating blood glucose levels. Circulating glucose affects intertemporal choice by means of signaling body energy condition instead of serving as a replenishing resource for effortful cognitive processing. We intend to dissociate calorie-supplying functions from glucose-unique anticipatory effects on behavioral resource management, measured by delay discounting in making intertemporal choices. Regarding the anticipatory functions of the glucose-insulin system in regulating the degree of delay discounting, we tested three predictions: First, we predict that the signaling effects of circulating glucose on delay discounting do not need to be dose-dependent as long as glucose fluctuation indicates a directional trend in body energy budget. Second, such effects of glucose fluctuation on delay discounting are phagic (appetite related) instead of dipsian (thirst related). Third, this glucose-insulin signaling system requires glucose as the specific input, thus is insensitive to other forms of sugar that are not insulin regulated. In Study 1, fasting participants were randomly assigned to one of five groups: water consumption, zero-consumption, and three glucose consumption (18 g, 36 g, and 72 g cane sugar/250 ml water) groups. The participants competed two sets of intertemporal choice questions with varying delay discounting rates before and after a beverage intervention. The results showed that the rate of delay discounting was negatively correlated to blood glucose levels. The effects of circulating glucose on delay discounting closely followed the changes in blood glucose levels showing a plateau on both dose-response curies (i.e., the sugar dose-blood glucose level curve and the sugar does-delay discounting curve). Secondly, the effects of circulating glucose on delay discounting were significant only in the glucose ingestion group, but not in the Zero consumption and the water consumption groups, suggesting that the behavioral effects were in fact related to hunger-reduction instead of thirst-reduction. Study 2 revealed that glucose ingestion, but not Water or another form of sugar (xylitol matched to glucose either for sweetness or for calories), reduced delay discounting, making future options more attractive. This result suggests that signaling of body energy budget is indeed glucose -unique. Our results suggest a forecasting mechanism of the glucose-insulin system for both metabolic and behavioral regulations of resource acquisition and allocation. (C) 2016 Elsevier Inc. All rights reserved.

Psychology Department.

 

Xu, Wenqin, & Elliott, Steven R. (2017). Solar axion search technique with correlated signals from multiple detectors.Astroparticle Physics, 89, 39-50.

The coherent Bragg scattering of photons converted from solar axions inside crystals would boost the signal for axion-photon coupling enhancing experimental sensitivity for these hypothetical particles. Knowledge of the scattering angle of solar axions with respect to the crystal lattice is required to make theoretical predications of signal strength. Hence, both the lattice axis angle within a crystal and the absolute angle between the crystal and the Sun must be known. In this paper, we examine how the experimental sensitivity changes with respect to various experimental parameters. We also demonstrate that, in a multiple-crystal setup, knowledge of the relative axis orientation between multiple crystals can improve the experimental sensitivity, or equivalently, relax the precision on the absolute solar angle measurement. However, if absolute angles of all crystal axes are measured, we find that a precision of 2 ∘ − 4 ∘ will suffice for an energy resolution of σ E = 0.04 E and a flat background. Finally, we also show that, given a minimum number of detectors, a signal model averaged over angles can substitute for precise crystal angular measurements, with some loss of sensitivity.

Physics Department.