Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep-proteome mapping of WM-266-4 human metastatic melanoma cells: From oncogenic addiction to druggable targets

Cutaneous melanoma is a malignant tumor of skin melanocytes that are pigment-producing cells located in the basal layer (stratum basale) of epidermis. Accumulation of genetic mutations within their oncogenes or tumor-suppressor genes compels melanocytes to aberrant proliferation and spread to distant organs of the body, thereby resulting in severe and/or lethal malignancy. Metastatic melanoma’s heavy mutational load, molecular heterogeneity and resistance to therapy necessitate the development of novel biomarkers and drug-based protocols that target key proteins involved in perpetuation of the disease. To this direction, we have herein employed a nano liquid chromatography-tandem mass spectrometry (nLC-MS/MS) proteomics technology to profile the deep-proteome landscape of WM-266-4 human metastatic melanoma cells. Our advanced melanoma-specific catalogue proved to contain 6,681 unique proteins, which likely constitute the hitherto largest single cell-line-derived proteomic collection of the disease. Through engagement of UNIPROT, DAVID, KEGG, PANTHER, INTACT, CYTOSCAPE, dbEMT and GAD bioinformatics resources, WM-266-4 melanoma proteins were categorized according to their sub-cellular compartmentalization, function and tumorigenicity, and successfully reassembled in molecular networks and interactomes. The obtained data dictate the presence of plastically inter-converted sub-populations of non-cancer and cancer stem cells, and also indicate the oncoproteomic resemblance of melanoma to glioma and lung cancer. Intriguingly, WM-266-4 cells seem to be subjected to both epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) programs, with 1433G and ADT3 proteins being identified in the EMT/MET molecular interface. Oncogenic addiction of WM-266-4 cells to autocrine/paracrine signaling of IL17-, DLL3-, FGF(2/13)- and OSTP-dependent sub-routines suggests their critical contribution to the metastatic melanoma chemotherapeutic refractoriness. Interestingly, the 1433G family member that is shared between the BRAF- and EMT/MET-specific interactomes likely emerges as a novel and promising druggable target for the malignancy. Derailed proliferation and metastatic capacity of WM-266-4 cells could also derive from their metabolic addiction to pathways associated with glutamate/ammonia, propanoate and sulfur homeostasis, whose successful targeting may prove beneficial for advanced melanoma-affected patients.
Underrepresented Minority Students in STEM Doctoral Programs: The Role of Financial Support and Relationships with Faculty and Peers.

Approved: ____________________________________ Thesis Supervisor ____________________________________ Title and Department ____________________________________ Date ____________________________________ Thesis Supervisor ____________________________________ Title and Department ____________________________________ Date 1 UNDERREPRESENTED MINORITY STUDENTS IN STEM DOCTORAL PROGRAMS: THE ROLE OF FINANCIAL SUPPORT AND RELATIONSHIPS WITH FACULTY AND PEERS by Margaret Nkirote Mwenda A thesis submitted in partial fulfillment of the requirements for the Doctor of Philosophy degree in Educational Policy and Leadership Studies in the Graduate College of The University of Iowa
Detection of Mycobacterium bovis in Bovine and Bubaline Tissues Using Nested-PCR for TbD1

In the present study, a nested-PCR system, targeting the TbD1 region, involving the performance of conventional PCR followed by real-time PCR, was developed to detect Mycobacterium bovis in bovine/bubaline tissue homogenates. The sensitivity and specificity of the reactions were assessed with DNA samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other actinomycetales species and DNA samples extracted directly from bovine and bubaline tissue homogenates. In terms of analytical sensitivity, the DNA of M. bovis AN5 was detected up to 1.56 ng with conventional PCR, 97.6 pg with real-time PCR, and 1.53 pg with nested-PCR in the reaction mixture. The nested-PCR exhibited 100% analytical specificity for M. bovis when tested with the DNA of reference strains of environmental mycobacteria and closely-related Actinomycetales. A clinical sensitivity value of 76.0% was detected with tissue samples from animals that exhibited positive results in the comparative intradermal tuberculin test (CITT), as well as from those with lesions compatible with tuberculosis (LCT) that rendered positive cultures. A clinical specificity value of 100% was detected with tissue samples from animals with CITT- results, with no visible lesions (NVL) and negative cultures. No significant differences were found between the nested-PCR and culture in terms of detecting CITT+ animals with LCT or with NVL. No significant differences were recorded in the detection of CITT- animals with NVL. However, nested-PCR detected a significantly higher number of positive animals than the culture in the group of animals exhibiting LCT with no previous records of CITT. The use of the nested-PCR assay to detect M. bovis in tissue homogenates provided a rapid diagnosis of bovine and bubaline tuberculosis.
Gelatin-Modified Polyurethanes for Soft Tissue Scaffold

Recently, in the field of biomaterials for soft tissue scaffolds, the interest of their modification with natural polymersis growing. Synthetic polymers are often tough, and many of them do not possess fine biocompatibility. On the other hand, natural polymers are biocompatible but weak when used alone. The combination of natural and synthetic polymers gives the suitable properties for tissue engineering requirements. In our study, we modified gelatin synthetic polyurethanes prepared from polyester poly(ethylene-butylene adipate) (PEBA), aliphatic 1,6-hexamethylene diisocyanate (HDI), and two different chain extenders 1,4-butanediol (BDO) or 1-ethoxy-2-(2-hydroxyethoxy)ethanol (EHEE). From a chemical point of view, we replaced expensive components for building PU, such as 2,6-diisocyanato methyl caproate (LDI) and 1,4-diisocyanatobutane (BDI), with cost-effective HDI. The gelatin was added in situ (in the first step of synthesis) to polyurethane to increase biocompatibility and biodegradability of the obtained material. It appeared that the obtained gelatin-modified PU foams, in which chain extender was BDO, had enhanced interactions with media and their hydrolytic degradation profile was also improved for tissue engineering application. Furthermore, the gelatin introduction had positive impact on gelatin-modified PU foams by increasing their hemocompatibility.
Leukotoxin Confers Beta-Hemolytic Activity to Actinobacillus actinomycetemcomitans

ABSTRACT Actinobacillus actinomycetemcomitans is the etiologic agent of localized aggressive periodontitis, a rapidly progressing oral disease that occurs in adolescents. A. actinomycetemcomitans can also cause systemic disease, including infective endocarditis. In early work on A. actinomycetemcomitans workers concluded that this bacterium is not beta-hemolytic. More recent reports have suggested that A. actinomycetemcomitans does have the potential to be beta-hemolytic. While growing A. actinomycetemcomitans on several types of growth media, we noticed a beta-hemolytic reaction on media from one manufacturer. Beta-hemolysis occurred on Columbia agar from Accumedia with either sheep or horse blood, but not on similar media from other manufacturers. A surprising result was that mutants of A. actinomycetemcomitans defective for production of leukotoxin, a toxin that is reportedly highly specific for only human and primate white blood cells, are not beta-hemolytic. Purified leukotoxin was able to lyse sheep and human erythrocytes in vitro. This work showed that in contrast to the accepted view, A. actinomycetemcomitans leukotoxin can indeed destroy erythrocytes and that the production of this toxin results in beta-hemolytic colonies on solid medium. In light of these results, the diagnostic criteria for clinical identification of A. actinomycetemcomitans and potentially related bacteria should be reevaluated. Furthermore, in studies on A. actinomycetemcomitans leukotoxin workers should now consider this toxin's ability to destroy red blood cells.
Rate-splitting multiple access for discrete memoryless channels

It is shown that the encoding/decoding problem for any asynchronous M-user discrete memoryless multiple-access channel can be reduced to corresponding problems for at most 2M-1 single-user discrete memoryless channels. This result, which extends a similar result for Gaussian channels, reduces the seemingly hard task of finding good multiple-access codes to the much better understood task of finding good codes for single-user channels. As a by-product, some interesting properties of the capacity region of M-user asynchronous discrete memoryless channels are derived.
Butyrate Transcriptionally Enhances Peptide Transporter PepT1 Expression and Activity

Background PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte. Results We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1) promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by ∼2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles. Conclusions Collectively, our results demonstrate that butyrate increases PepT1 expression and activity in colonic epithelial cells, which provides a new understanding of PepT1 regulation during chronic inflammation.
Performance Study of Organization and Data Aggregation in Wireless Sensor Networks

In this paper, we analyze clustering in large sensor networks, as a way to address high redundancy of measured data. We are in particular interested in approach, in which sensor nodes organize themselves into data-aggregation clusters based on the measured magnitude (t) of an observed physical phenomenon (T ) as follows: at any given time, all the sensors whose measured t belongs to the interval (tm − ∆T, tm + ∆T ) are grouped in the same logical cluster. Here tm is the mean value measured within the cluster and ∆T is the predefined query-specific precision (fidelity) interval. Sensors conceptually ”move” between logical clusters when their measured values change. Energy efficiency may be achieved if only one sensor within each cluster reports aggregated information to the sink node. The results of our performance study in an event-based simulation environment, show that clustering is a promising approach however it requires application specific data handling.
Experimental Studies of Virtual Reality-Delivered Compared to Conventional Exercise Programs for Rehabilitation

This paper presents preliminary data from two clinical trials currently underway using flat screen virtual reality (VR) technology for physical rehabilitation. In the first study, we are comparing a VR-delivered exercise program to a conventional exercise program for the rehabilitation of shoulder joint range-of-motion in patients with chronic frozen shoulder. In the second study, we are comparing two exercise programs, VR and conventional, for balance retraining in subjects post-traumatic brain injury. Effective VR-based rehabilitation that is easily adapted for individuals to use both in inpatient, outpatient and home-based care could be used as a supplement or alternative to conventional therapy. If this new treatment approach is found to be effective, it could provide a way to encourage exercise and treatment compliance, provide safe and motivating therapy and could lead to the ability to provide exercises to clients in distant locations through telehealth applications of VR treatment. VR is a new technology and the possibilities for rehabilitation are only just beginning to be assessed.
Strategic Market Making and Risk Sharing

We analyze the result of allowing a risk averse trader to split his order among risk averse market makers. We find that the market makers’ aggregate expected utility of profit can increase with the number of market markers and that the aggregate liquidity always increases with it. Despite this latter finding, we show that the cost of trading for the traders increases with the number of market makers as measured by their aggregate expected utility of profit. The larger the market makers’ risk aversion, the bigger that cost is. We also find that when the number of market makers tends to infinity, their aggregate expected utility of profit tends to zero. We also obtain that the market makers’ individual and aggregate expected utility of profit can increase with their risk aversion and that the trader’s expected utility of profit can increase or decrease with the market makers’ risk aversion. We offer a potential answer to the ongoing debate concerning the dealers’ competitiveness. Indeed, risk aversion reduces competition between market makers as it acts as a commitment for market makers to set higher prices. This commitment is higher the higher the risk aversion.
Active longitudes, nonaxisymmetric dynamos and phase mixing

We discuss the problem of solar active longitudes from the viewpoint of dynamo theory. We start from a recent observational analysis of the problem undertaken by Berdyugina & Usoskin (2003, AA however we can not exclude in principle such an explanation. We relate the phenomenon of solar active longitudes to the information available concerning stellar active longitudes, and also consider evidence from other tracers of solar activity.
Consumption Growth and the Real Interest Rate following a Monetary Policy Shock: Is the Habit Persistence Assumption Relevant?

In this paper, we study the role of habit formation in accounting for the joint behavior of the real interest rate and consumption growth following a contractionary monetary policy shock, the real interest rate exhibits a persistent increase while consumption growth drops persitently. As the standard permanent income model is known to be unable to replicate this co-movement for intertemporal substitution motives, we introduce habit persistence in consumption behavior. We test the implied Euler equation using a method of moments on conditional moments (IRF) obtained from the VAR Model. Our estimates of the habit persistence parameter are similar to previous results in the literature. Further, we find empirical support in favor of habit formation as a relevant assumption to represent the joint behavior of the real interest rate and the consumption growth following a monetary policy shock. Finally, we show that habit formation allows weakening the intertemporal substitution mechanism
Lack of association between folate-receptor autoantibodies and neural-tube defects.

BACKGROUND A previous report described the presence of autoantibodies against folate receptors in 75% of serum samples from women with a history of pregnancy complicated by a neural-tube defect, as compared with 10% of controls. We sought to confirm this finding in an Irish population, which traditionally has had a high prevalence of neural-tube defects. METHODS We performed two studies. Study 1 consisted of analysis of stored frozen blood samples collected from 1993 through 1994 from 103 mothers with a history of pregnancy complicated by a neural-tube defect (case mothers), 103 mothers with a history of pregnancy but no complication by a neural-tube defect (matched with regard to number of pregnancies and sampling dates), 58 women who had never been pregnant, and 36 men. Study 2, conducted to confirm that the storage of samples did not influence the folate-receptor autoantibodies, included fresh samples from 37 case mothers, 22 control mothers, 10 women who had never been pregnant, and 9 men. All samples were assayed for blocking and binding autoantibodies against folate receptors. RESULTS In Study 1, blocking autoantibodies were found in 17% of case mothers, as compared with 13% of control mothers (odds ratio, 1.54; 95% confidence interval [CI], 0.70 to 3.39), and binding autoantibodies in 29%, as compared with 32%, respectively (odds ratio, 0.82; 95% CI, 0.44 to 1.50). Study 2 showed similar results, indicating that sample degradation was unlikely. CONCLUSIONS The presence and titer of maternal folate-receptor autoantibodies were not significantly associated with a neural-tube defect-affected pregnancy in this Irish population.
Effect of Lamivudine on the Plasma and Intracellular Pharmacokinetics of Apricitabine, a Novel Nucleoside Reverse Transcriptase Inhibitor, in Healthy Volunteers

ABSTRACT Apricitabine is a novel deoxycytidine analog reverse transcriptase inhibitor. In vitro apricitabine competes with other deoxycytidine analogues for intracellular phosphorylation mediated by deoxycytidine kinase. The topic of this study, the effect of concomitant administration of apricitabine and lamivudine on the plasma and intracellular pharmacokinetics of the two compounds, was investigated in healthy volunteers. Participants (n = 21; age, 18 to 30 years) received apricitabine at 600 mg twice daily, lamivudine at 300 mg once daily, and the two treatments in combination for 4 days each in random order. Plasma, urine, and intracellular pharmacokinetics were assessed on day 4 of each treatment period. Apricitabine was rapidly absorbed after oral administration, with peak concentrations being attained after a mean of 1.76 h. Coadministration with lamivudine had no significant effect on the plasma and urine pharmacokinetics of apricitabine. However, the formation of apricitabine triphosphate in peripheral blood mononuclear cells was markedly reduced after the coadministration of apricitabine and lamivudine than after the administration of apricitabine alone: the area under the concentration-time curve from 0 to 12 h for apricitabine triphosphate during combination treatment was ca. 15% of that seen after the administration of apricitabine alone. In contrast, apricitabine had no effect on the plasma pharmacokinetics of lamivudine or on the formation of lamivudine triphosphate in peripheral blood mononuclear cells. These results are consistent with in vitro findings that lamivudine inhibits the intracellular phosphorylation of apricitabine. In conjunction with similar in vitro observations for emtricitabine and apricitabine, these results suggest that apricitabine should not be coadministered with other deoxycytidine analogues for the treatment of human immunodeficiency virus infection.
Bank Bailouts, Interventions, and Moral Hazard

To test if safety nets create moral hazard in the banking industry, we develop a simultaneous structural two-equations model that specifies the probability of a bailout and banks' risk taking.We identify the effect of expected bailout probabilities on risk taking using exclusion restrictions based on regional political, supervisor, and banking market traits. The sample includes all observed capital preservation measures and distressed exits in the German banking industry during 1995-2006. The marginal effect of risk with respect to bailout expectations is 7.2 basis points. A change of bailout expectations by two standard deviations increases the probability of official distress from 6.2% to 9.9%. Only interventions directly targeting bank management and, to a lesser extent, penalties mitigate moral hazard. Weak interventions, such as warnings, do not reduce moral hazard.
"Everything's There Except Money": How Economic Factors Shape the Decision to Marry Among Cohabiting Couples*

Unmarried cohabitation has become increasingly prominent in the United States and a growing literature has sought to understand the factors that spur cohabiting couples to marry. While quantitative studies suggest that good economic circumstances are associated with marriage, the mechanisms and the sequencing through which economics influence marriage are less well understood. Drawing on data from 115 in-depth interviews with cohabiting young adults from the working and middle classes, this paper explores whether and in what ways economic circumstances shape perspectives on marriage. We find that cohabitors typically perceive finances as important for marriage, with common themes including having “enough” money, being able to afford a “real” wedding, having achieved a set of financial goals prior to marriage (e.g., home ownership, financial stability), and the ability of the male partner to be an economic provider. While some social scientists have speculated that cohabitors must think that something will change in their lives in order to motivate marriage, our findings suggest that cohabitors think marriage should occur once something has already changed; that is, marriage does not mean that you are working to become financially comfortable, but that you already are. INTRODUCTION As is well known, the last few decades have ushered in significant changes in family patterns -in union formation, union dissolution, childbearing, and attitudes about a range of family issues (Casper & Bianchi, 2002; Thornton, Fricke, Axinn, & Alwin 2001; Thornton & Young-Demarco, 2001). After a brief period characterized by early marriage and low levels of divorce after World War II (during the Baby Boom), recent decades have been marked by lower levels of childbearing, higher divorce rates, increases in the average age at marriage, rising nonmarital childbearing, and rising levels of cohabitation. Although most Americans still marry at some point and the vast majority express strong desires to marry, unmarried cohabitation has dramatically transformed the marriage process. Today, the majority of marriages and remarriages begin as cohabiting relationships. Most young men and women have cohabited or will cohabit, cohabitation has increased in all age groups, and cohabitation is increasingly becoming a context for childbearing and childrearing. In fact, it is estimated that two-fifths of children born in the early 1990s will spend time in a cohabitingparent family (Bumpass & Lu, 2000; Casper & Bianchi, 2002; Chevan, 1996; Manning, 2002). Given that cohabitation is now the modal path to marriage, an important issue is whether and under what circumstances cohabitation leads to marriage. A long line of research in the social sciences has drawn on data from surveys or the Census to examine the economic determinants of marriage. More recently, studies have emerged examining similar issues for cohabiting unions (e.g., Brown, 2000; Clarkberg, 1999; Manning & Smock, 1995; Oppenheimer, 2003; Sassler & McNally, 2003; Smock & Manning, 1997; Wu & Pollard, 2000).