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In this study the mouse tumor necrosis factor-alpha (TNF-α) was prepared by stimulating macrophage cell line RAW 264.7 with lipopoly-saccharide (LPS) obtained from Escheria coli strain 055:B5.

Journal impact factors play an increasing role in academics as a tool for evaluating faculty, research, and resource allocations. These evaluations may be effective in departments where the subject matter is reasonably unified. However, given the diversity found within the subject matter of psychology, the impact factors of journals may not be comparable across the various areas. This study compares the average impact factors across decile levels of journals from seven areas of psychology. It is found that impact factor scores are not comparable across the seven areas of psychology. This difference is more pronounced when looking at higher decile journals. Further research could be conducted to investigate differences among psychology areas using other bibliographic variables, including some of the newer indices of individual scholar productivity, such as the h-index.

With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases the binding to the Stat3 SH2 domain. Evidence is presented from in vitro biochemical and biophysical studies that S3I-201.1066 directly interacts with Stat3 or the SH2 domain, with an affinity (K[subscript D]) of 2.74 [micrometer], and disrupts the binding of Stat3 to the cognate pTyr-peptide, GpYLPQTV-NH2, with an IC₅₀ of 23 [micrometer]. Moreover, S3I-201.1066 selectively blocks the association of Stat3 with the epidermal growth factor receptor (EGFR), and inhibits Stat3 tyrosine phosphorylation and nuclear translocation in EGF-stimulated mouse fibroblasts. In cancer cells that harbor aberrant Stat3 activity, S3I-201.1066 inhibits constitutive Stat3 DNA-binding and transcriptional activities. By contrast, S3I-201.1066 has no effect on Src activation or the EGFR-mediated activation of the Erk1/2MAPK pathway. S3I-201.1066 selectively suppresses the viability, survival, and malignant transformation of the human breast and pancreatic cancer lines and the v-Src-transformed mouse fibroblasts harboring persistently active Stat3. Treatment with S3I-201.1066 on malignant cells harboring aberrantly active Stat3 down regulated the expression of c-Myc, Bcl-xL, Survivin, matrix metalloproteinase 9, and VEGF, which are known Stat3-regulated genes important in diverse tumor processes. The in vivo administration of S3I-201.1066 induced significant anti-tumor response in mouse models of human breast cancer, which correlates with the inhibition of constitutively active Stat3 and the suppression of known Stat3-regulated genes. Further computer-aided lead optimization derives higher-affinity (K[subscript D], 504 nM), orally bioavailable Stat3 SH2 domain-binding ligand, BP-1-102 as a structural analog of S3I-201.1066. The most significant modification is the pentafluorobenzene sulfonamide component of BP-1-102, which permits accessibility of a third sub-pocket of the Stat3 SH2 domain surface. BP-1-102-mediated inhibition of aberrantly-active Stat3 in human pancreatic cancer, Panc-1, breast cancer, MDA-MB-231, and prostate (DU145) cancer cells and in the mouse transformed fibroblasts harboring aberrantly-active Stat3. It also disrupts Stat3-NF[kappa]B cross-talk and suppresses the release of granulocyte colony-stimulating factor, soluble intercellular adhesion molecule-1, macrophage-migration-inhibitory factor/glycosylation-inhibiting factor, interleukin-1 receptor antagonist and the serine protease inhibitor (serpin) protein 1, and the expression of c-Myc, Cyclin D1, Bcl-xL, Survivin, and vascular endothelial growth factor expression in vitro and in vivo. Inhibition of tumor cell-associated constitutively-active Stat3 further suppresses focal adhesion kinase and paxillin induction, enhances E-cadherin expression, and down-regulates Kruüppel-like factor 8 expression. Consequently, BP-1-102 selectively suppresses anchorage-dependent and independent growth, survival, migration and invasion of Stat3-dependent tumor cells in vitro. Intravenous or oral gavage delivery of BP-1-102 furnishes micromolar or microgram levels in tumor tissues and inhibits growth of mouse xenografts of human breast and lung tumors. Computer-aided lead optimization has therefore derived a more suitable small-molecule inhibitor as a drug candidate. Our studies of the Stat3 SH2 protein surface and of the interactions between lead agents and the SH2 domain provided significant data to facilitate the structural optimization. From S2I-201 to S3I-201.1066 and to BP-1-102, we note the substantial gain in potency and efficacy, and the pharmacokinetic improvements. The oral bioavailability of BP-1-102 represents a substantial advancement in the discovery of small-molecule Stat3 inhibitors as novel anticancer agents.

OBJECTIVE: Diverticular bleeding is the most common cause of lower gastrointestinal bleeding. Arteriovascular disease, metabolic syndromes, non-steroidal anti-inflammatory drugs (NSAIDs), anti-thrombotics, and anticoagulants have been suggested as risk factors. There is a paucity of studies addressing factors associated with diverticular re-bleeding, especially in the United States. The aim of this study is to evaluate factors associated with colonic diverticular bleeding and re-bleeding in a US community-based hospital. METHODS: We conducted a retrospective case-control study to analyze the factors associated with diverticular bleeding. Between January 2010 and July 2011, 93 patients were admitted to our hospital with a primary diagnosis of acute diverticular bleeding. We compared them to 152 patients who were admitted with a primary diagnosis of diverticulitis in the same period. We collected data from the medical records of each patient in relation to the demographics, comorbidities, medications, social habits, location of diverticulosis, length of stay in the hospital, and re-bleeding rate within 2 years of the first bleeding episode. RESULTS: Factors such as cerebrovascular accident (p=0.009), coronary artery disease (p=0.037), diabetes mellitus (p=0.046), obstructive sleep apnea (p=0.033), NSAIDs (p=0.038), use of anti-thrombotics (p=0.001), anticoagulants (p=0.002) or calcium channel blockers (p=0.009), and bilateral diverticulosis (p=0.001) were significantly associated with diverticular bleeding as compared to diverticulitis. Recurrence of bleeding was noted in 26 out of 93 patients (28%) within 2 years of the first bleeding episode (p=0.001). Bilateral colonic involvement, anticoagulants, and elderly age (≥65 years) were found to have a closer relationship to diverticular re-bleeding, although it was not statistically significant. CONCLUSION: This study reveals that arteriovascular disease, diabetes mellitus, NSAIDs, the use of anti-thrombotics, anticoagulants or calcium channel blockers, and obstructive sleep apnea are factors that are significantly associated with diverticular bleeding. It also shows that bilateral colonic involvement, elderly age, and anticoagulants have a closer relationship to diverticular re-bleeding. More prospective studies in patients with diverticular bleeding should be conducted to shed light on the causality of these factors and the prevalence of diverticulitis.

When exposed to either abiotic or biotic stressors, plants release chemical compounds that can serve as defense mechanisms. For example, plants of the mustard and cabbage family produce a class of anti-herbivory compounds called glucosinolates. In the model mustard plant Arabidopsis thaliana, some glucosinolates are produced from the amino acid tryptophan and are called indole glucosinolates (IGs). Expression of IG synthesis genes is positively regulated by the partially redundant transcription factors, MYB34 and MYB51. Recent studies have shown that these two transcription factors have distinct roles in regulating IG production in different tissues and in mediating responses to different environmental cues. To understand the distinct roles of these transcription factors at a more detailed temporal and spatial level, reporters for CYP79B2, a transcriptional target of both MYB34 and MYB51, were used. CYP79B2-GFP and CYP79B2-GUS reporter expression was analyzed in wild-type and MYB34 and MYB51 mutant plants in response to increased ambient temperature, increased light intensity, ATP exposure, and chitin exposure. Reverse-phase HPLC quantification of IGs was also performed to determine how these transcription factors are mediating the synthesis of IGs in response stressors. Overall, it was found that MYB51 is responsible for the temperature induction of IG production, while increased light intensity has no impact on IG synthesis. Furthermore, ATP appears to induce IG production independently of both MYB34 and MYB51, while chitin does not increase IG synthesis. Taken together, these studies allow us to better understand how plants respond to and defend themselves from different abiotic and biotic stress / 2025-02-26T00:00:00Z

<p> A report follows in which five different conditions of support of stepped crane columns were investigated. In each case the curvature or moment equations representing the column in its just-buckled condition are determined. The general solution of each differential equation is then found and solved in terms of the boundary conditions to obtain a transcendental equation which gives the critical buckling length. This transcendental equation is solved for the lowest possible value to get the critical buckling length. This lowest value is compared to the Euler critical buckling value in order to get the effective length factor.</p> / Thesis / Master of Engineering (MEngr)

The primary purpose of this study was to confirm the four-factor structure of the 30-item Adlerian Personality Priority Assessment (APPA) using a split-sample cross-validation confirmatory factor analysis (CFA). The APPA is an assessment, grounded in Adlerian theory, used to conceptualize clients based on the four personality priorities most commonly used in the Adlerian literature: superiority, pleasing, control, and comfort. The secondary purpose of this study was to provide evidence for discriminant validity, examine predictive qualities of demographics, and explore the prevalence of the four priorities across demographics. For the cross validation CFA, I randomly divided the sample, 1210 undergraduates, at a large public research university (53% Caucasian, 13.1% Hispanic/Latino(a), 21.4% African American, 5.4% American Indian, and 5.8% biracial; mean age =19.8; 58.9% females), into two equal subsamples. I used Subsample 1 (n = 605) to conduct the initial CFA. I held out Subsample 2 (n = 605) to test any possible model changes resulting from Subsample 1 results and to provide further confirmation of the APPA's construct validity. Findings from the split-sample cross-validation CFA confirmed the four-factor structure of the APPA and provided support for the factorial/structure validity of the APPA's scores. Results also present initial evidence of discriminant validity and support the applicability of the instrument across demographics. Overall, these findings suggest Adlerian counselors can confidently use the APPA as a tool to conceptualize clients.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).