Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated transcriptomic and proteomic analysis identifies protein kinase CK2 as a key signaling node in an inflammatory cytokine network in ovarian cancer cells

We previously showed how key pathways in cancer-related inflammation and Notch signaling are part of an autocrine malignant cell network in ovarian cancer. This network, which we named the “TNF network”, has paracrine actions within the tumor microenvironment, influencing angiogenesis and the immune cell infiltrate. The aim of this study was to identify critical regulators in the signaling pathways of the TNF network in ovarian cancer cells that might be therapeutic targets. To achieve our aim, we used a systems biology approach, combining data from phospho-proteomic mass spectrometry and gene expression array analysis. Among the potential therapeutic kinase targets identified was the protein kinase Casein kinase II (CK2). Knockdown of CK2 expression in malignant cells by siRNA or treatment with the specific CK2 inhibitor CX-4945 significantly decreased Notch signaling and reduced constitutive cytokine release in ovarian cancer cell lines that expressed the TNF network as well as malignant cells isolated from high grade serous ovarian cancer ascites. The expression of the same cytokines was also inhibited after treatment with CX-4945 in a 3D organotypic model. CK2 inhibition was associated with concomitant inhibition of proliferative activity, reduced angiogenesis and experimental peritoneal ovarian tumor growth. In conclusion, we have identified kinases, particularly CK2, associated with the TNF network that may play a central role in sustaining the cytokine network and/or mediating its effects in ovarian cancer.
On w-mixtures: Finite convex combinations of prescribed component distributions

We consider the space of $w$-mixtures which is defined as the set of finite statistical mixtures sharing the same prescribed component distributions closed under convex combinations. The information geometry induced by the Bregman generator set to the Shannon negentropy on this space yields a dually flat space called the mixture family manifold. We show how the Kullback-Leibler (KL) divergence can be recovered from the corresponding Bregman divergence for the negentropy generator: That is, the KL divergence between two $w$-mixtures amounts to a Bregman Divergence (BD) induced by the Shannon negentropy generator. Thus the KL divergence between two Gaussian Mixture Models (GMMs) sharing the same Gaussian components is equivalent to a Bregman divergence. This KL-BD equivalence on a mixture family manifold implies that we can perform optimal KL-averaging aggregation of $w$-mixtures without information loss. More generally, we prove that the statistical skew Jensen-Shannon divergence between $w$-mixtures is equivalent to a skew Jensen divergence between their corresponding parameters. Finally, we state several properties, divergence identities, and inequalities relating to $w$-mixtures.
Investigating predictors of eating: is resting metabolic rate really the strongest proxy of energy intake?

Background: Evidence suggests that fat-free mass and resting metabolic rate (RMR), but not fat mass, are strong predictors of energy intake (EI). However, body composition and RMR do not explain the entire variance in EI, suggesting that other factors may contribute to this variance.Objective: We aimed to investigate the associations between body mass index (in kg/m2), fat mass, fat-free mass, and RMR with acute (1 meal) and daily (24-h) EI and between fasting appetite ratings and certain eating behavior traits with daily EI. We also evaluated whether RMR is a predictor of the error variance in acute and daily EI.Design: Data collected during the control condition of 7 studies conducted in Ottawa, Ontario, Canada, were included in these analyses (n = 191 and 55 for acute and daily EI, respectively). These data include RMR (indirect calorimetry), body composition (dual-energy X-ray absorptiometry), fasting appetite ratings (visual analog scales), eating behavior traits (Three-Factor Eating Questionnaire), and EI (food buffet or menu). Results: Fat-free mass was the best predictor of acute EI (R2 = 0.46; P < 0.0001). The combination of fasting prospective food consumption ratings and RMR was the best predictor of daily EI (R2 = 0.44; P < 0.0001). RMR was a statistically significant positive predictor of the error variance for acute (R2 = 0.20; P < 0.0001) and daily (R2 = 0.23; P < 0.0001) EI. RMR did, however, remain a statistically significant predictor of acute (R2 = 0.32; P < 0.0001) and daily (R2 = 0.30; P < 0.0001) EI after controlling for this error variance.Conclusions: Our findings suggest that combined measurements of appetite ratings and RMR could be used to estimate EI in weight-stable individuals. However, greater error variance in acute and daily EI with increasing RMR values was observed. Future studies are needed to identify whether greater fluctuations in daily EI over time occur with increasing RMR values. This trial was registered at clinicaltrials.gov as NCT02653378.
A Phase II, Open-Label, Randomized Study to Assess the Efficacy and Safety of AZD6244 (ARRY-142886) Versus Pemetrexed in Patients with Non-small Cell Lung Cancer Who Have Failed One or Two Prior Chemotherapeutic Regimens

Introduction: AZD6244 (ARRY-142886) is a potent, selective MEK inhibitor. This study aimed to evaluate the efficacy and safety of AZD6244 versus pemetrexed as second- or third-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Methods: In this randomized phase II study, patients received either 100 mg oral AZD6244 free-base suspension twice daily or 500 mg/m2 intravenous pemetrexed once every 3 weeks after pretreatment with a corticosteroid, folic acid, and vitamin B12. The primary end point of the study was the disease progression event count. Results: Eighty-four patients were randomized. Disease progression events were experienced by 28 (70%) and 26 (59%) patients in the AZD6244 and pemetrexed groups, respectively. Median progression-free survival was not statistically significantly different between the AZD6244 and pemetrexed groups (67 versus 90 days, respectively; hazard ratio 1.08, two-sided 80% confidence interval = 0.75–1.54; p = 0.79). Two patients in the AZD6244 group had a best response to treatment of partial response. In the pemetrexed group, one patient achieved a complete response and one patient a partial response. Dermatitis acneiform, diarrhea, nausea, and vomiting were the most frequently reported adverse events with AZD6244, compared with fatigue, anemia, nausea, anorexia, and dermatitis acneiform with pemetrexed. Conclusions: Oral AZD6244 showed clinical activity as second- or third-line therapy for patients with advanced NSCLC. In an unselected NSCLC population, there is no suggestion that AZD6244 monotherapy offers any advantage over standard treatment with pemetrexed. Based on preclinical data and recent clinical observations, further development of AZD6244 in NSCLC should focus on BRAF or RAS mutation-positive patients and/or AZD6244-based combination regimens.
Transcriptional Repression Mediated by LysR-Type Regulator CatR Bound at Multiple Binding Sites

ABSTRACT The catBCA operon of Pseudomonas putidaencodes enzymes involved in the catabolism of benzoate. Transcription of this operon requires the LysR-type transcriptional regulator CatR and an inducer molecule, cis,cis-muconate. Previous gel shift assays and DNase I footprinting have demonstrated that CatR occupies two adjacent sites proximal to thecatBCA promoter in the presence of the inducer. We report the presence of an additional binding site for CatR downstream of thecatBCA promoter within the catB structural gene. This site, called the internal binding site (IBS), extends from +162 to +193 with respect to the catB transcriptional start site and lies within the catB open reading frame. Gel shift analysis and DNase I footprinting determined that CatR binds to this site with low affinity. CatR binds cooperatively with higher affinity to the IBS in the presence of the two upstream binding sites. Parallel in vivo and in vitro studies were conducted to determine the role of the internal binding site. We measured β-galactosidase activity ofcatB-lacZ transcriptional fusions in vivo. Our results suggest a probable cis-acting repressor function for the internal binding site. Site-directed mutagenesis of the IBS verified this finding. The location of the IBS within the catBstructural gene, the cooperativity observed in footprinting studies, and phasing studies suggest that the IBS likely participates in the interaction of CatR with the upstream binding sites by looping out the intervening DNA.
Rat embryonic fibroblasts immortalized by MRPS18-2 protein are target for NK-cells

Overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts (REFs). The derived cells (18IM) expressed embryonic stem cell markers. Noteworthy, genes encoding the COX family proteins were up-regulated significantly. It is known that the COX family proteins are involved in the regulation of immune response. In the present work we demonstrate that 18IM cells behave like stem cells when subjected to directed differentiation in vitro. However, unlike stem cells, 18IM cells do not develop tumors in vivo, in SCID mice. This phenomenon is observed due to the strong natural killer (NK) cell immunogenicity. 18IM cells were better recognized by NK cells, compared with primary REFs, as was shown by a standard NK killing assay. Our data explain asymmetry in behavior of stem-like cells in vivo and in vitro, and this support the notion that stem and/or cancer-initiating cells are preferred targets for NK-cells. Concluding, the S18-2 protein is a putative target for cancer vaccines.
Synchronization of delayed multi-agent systems over uncertain networks

This paper is concerned with the mean square exponential (MSE) synchronization problem for the multi-agent systems with time delays over uncertain networks, where the uncertainty lies in that the links between subsystems are varying stochastically according to certain rules. Firstly, applying the theories of coordinate transformation, Kronecker product and Laplacian matrix, the synchronization problem for the addressed multi-agent systems is transformed into investigating the exponential stability in the mean square for a modified system. Then, by constructing an appropriate Lyapunov functional, sufficient criteria are derived which assure the MSE stability of the transformed system, and hence guarantee the MSE synchronization of the original multi-agent systems. Moveover, through decomposing the transformed system, an easy-to-check sufficient condition is given which is based on the relationships between the system parameters of the single agent, the network topology and the statistical characterizations of the network uncertainties. Simulation examples are presented in the end of the paper to demonstrate the validity of the obtained results.
Class I Rab11‐family interacting proteins are binding targets for the Rab14 GTPase

Background information. Rab11 and Rab14 are two related Rab GTPases that are believed to function in endosomal recycling and Golgi/endosome transport processes. We, and others, have identified a group of proteins that interact with Rab11 and function as Rab11 effectors, known as the Rab11‐FIPs (family interacting proteins). This protein family has been sub‐classified into two groups—class I FIPs [FIP2, RCP (Rab coupling protein) and Rip11 (Rab11‐interacting protein)] and class II FIPs (FIP3 and FIP4).
Transplantation of Adipose Tissue-Derived Stromal Cells Increases Mass and Functional Capacity of Damaged Skeletal Muscle

The regenerating skeletal muscle environment is capable of inducing uncommitted progenitors to terminally differentiate. The aim of this work was to determine whether adipose tissue-derived stromal cells were able to participate in muscle regeneration and to characterize the effect on muscle mass and functional capacities after transplantation of these cells. Adipose tissue stromal cells labeled with Adv cyto LacZ from 3-day-old primary cultures (SVF1) were autotransplanted into damaged tibialis anterior muscles. Fifteen days later, β-galactosidase staining of regenerated fibers was detected, showing participation of these cells in muscle regeneration. Two months after SVF1 cell transfer, muscles were heavier, showed a significantly larger fiber section area, and developed a significantly higher maximal force compared with damaged control muscles. These results are similar to those previously obtained after satellite cell transplantation. However, SVF1 transfer also generated a small amount of adipose tissue localized along the needle course. To minimize these adipose contaminants, we transferred cells from 7-day-old secondary cultures of the SVF1, containing only a small proportion of already engaged preadipocytes (SVF2). Under these conditions, no adipose tissue was observed in regenerated muscle but there was also no effect on muscle performances compared with damaged control muscles. This result provides further evidence for the existence of progenitor cells in the stromal fraction of freshly isolated adipose tissue cells, which, under our conditions, keep some of their pluripotent properties in primary cultures.
Can you hear me now? Limited use of technology among an urban HIV-infected cohort

Abstract Recent studies support technology-based behavioral interventions for individuals with HIV. This study focused on the use of cell phone and internet technologies among a cohort of 515 HIV-infected individuals. Socio-demographic and clinic data were collected among individuals presenting at an urban Midwestern university HIV clinic in 2007. Regular internet usage occurred more often with males, Caucasians, those who were employed, had higher income, and were more educated. Higher levels of education and income >$10,000 predicted regular usage when controlling for race, employment, and gender. Cell phone ownership was associated with being Caucasian, employed, more educated, and salary >$10,000. Employment was the only predictor of owning a cell phone when controlling for income, race, and education. Individuals who were <40 years of age, employed, and more educated were more likely to know how to text message. Employment and post-high school education predicted knowledge of text messaging, when controlling for age. Disparities among internet, cell phone, and text messaging usage exist among HIV-infected individuals.
An Effective Defect Inspection Method for LCD Using Active Contour Model

Visual defects in liquid crystal display images often appear as low contrast and blurry contour without distinct intensity difference from their surrounding region. Besides, the background is usually intensity inhomogeneity. All these properties make the machine vision inspection extremely hard. This paper presents an effective machine vision inspection method using a local active contour model to detect defects with different brightness levels as well as diverse sizes and shapes. A modified local binary fitting model which is robust to initial contour is developed to extract defect boundary. Meanwhile, a simple preprocessing scheme is given to compensate the drawback of the two-phase active contour model for detecting objects with wide brightness levels. Experimental results show that the presented method can detect various types of defects effectively and achieves high performance in terms of inspection accuracy (both precision and recall are higher than 0.99).
Qualitative evaluation of visibility enhancement techniques on SAMEER-TU database for security and surveillance

Computer vision applications such as surveillance, topography categorization, and independent navigation need accurate detection of image features and hence requires clear visibility. But the images captured in outdoor scenes are usually degraded by the particles in the atmosphere and hence loses the contrast and color fidelity. The paper presents a significant methodological review on different categories of visibility enhancement techniques in weather degraded outdoor scenes and provides comprehensive descriptions of various representative methods in each of this category. Based on the rigorous review of these publications, the paper also explores a comparative analysis of some prominent image enhancement techniques for visibility restoration in our own SAMEER-TU database to verify the robustness of these used methods.
Have Post-Kelo Restrictions on Eminent Domain Influenced State Economic Development?

In 2005, the Supreme Court’s Kelo v. New London ruling reaffirmed governments’ right to use eminent domain for economic development purposes. Widespread public backlash over the ruling resulted in numerous states quickly passing laws restricting the use of eminent domain for such purposes. This study uses the swift and uneven response of state legislatures to the public outcry that followed Kelo to test the empirical question of whether restrictions on eminent domain affect states’ ability to fulfill their economic development goals. Results indicate that states that restricted the use of eminent domain following the Kelo ruling experienced no adverse effects in terms of state employment and gross state product or county employment and county income in the states’ most dense counties.
A Prospective Study of Exercise-Associated Hyponatremia in Two Ultradistance Triathletes

ObjectiveTo study fluid and sodium balance in two ultradistance triathletes. DesignProspective case study. SettingAn ultradistance triathlon (3.8 km swim, 180 km cycle, 42.2 km run), and during overnight recovery. Ambient air temperature at 12:00 p.m. race day was 21°C, with a relative humidity of 91%. Water temperature was 20.7°C. SubjectsTwo female ultradistance triathletes, ages 30 and 39 years, who were participating in a larger study investigating weight and electrolyte changes in the Ironman triathlon. InterventionsNone. Main Outcome MeasuresSubjects were weighed and had blood drawn for serum sodium concentration, hemoglobin, hematocrit, arginine vasopressin, and aldosterone concentration prior to and after the race, and at 8:00 a.m. the following morning. Sodium and fluid intake and urinary output were measured during recovery. ResultsBoth subjects developed mild hyponatremia (Na 131 and 130 mmol/L) during the race, with a weight gain (0.5 and 1.5 kg). Neither subject had large sodium losses (24 mmol and 20 mmol). Fluid consumption was 733 ml/h and 764 ml/h. Plasma volume increased during the race (25 and 16%). Arginine vasopressin (AVP) levels were not elevated in either subject (1.2 and 1.9 pmol/L). Both subjects demonstrated a water excess during the race (1.5 and 2.5 L), and lost weight during recovery (2.0 and 4.5 kg). ConclusionsHyponatremia resulted from fluid retention in the extracellular space, without evidence of large sodium losses or inappropriate AVP secretion.
Subjective perception of sleep, but not its objective quality, is associated with immediate postpartum mood disturbances in healthy women.

STUDY OBJECTIVES This study investigated whether there was a relationship between disrupted sleep and postpartum mood disturbances in women during the week after delivery. DESIGN Sleep and mood were measured during the third trimester (Time-1) and one week postpartum (Time-2) in a 2-stage longitudinal design. SETTING Participants were recruited from an antenatal clinic in a regional Melbourne hospital. PARTICIPANTS Forty-four healthy women at low risk for postpartum depression. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Objective sleep was measured by actigraphy and subjective sleep by the Pittsburgh Sleep Quality Index; mood was assessed by the Depression Anxiety Stress Scale, the Hospital Anxiety Depression Scale, and the Positive and Negative Affect Schedule. Sleep and mood questionnaires were administered at Time-1 and Time-2. Wrist actigraphy was collected for one week at both times. After delivery, both objective and subjective nighttime sleep significantly worsened with decreased total sleep time and sleep efficiency, while daytime napping behavior significantly increased. On average, mood improved across all scales after delivery, although 45.95% of the sample experienced deterioration of mood. Regression analyses showed little relationship between Time-1 and Time-2 objective nighttime sleep, and postpartum mood. Variables that related to both Time-1 and Time-2 subjective perception of sleep, including subjective nighttime sleep, sleep-related daytime dysfunction, and daytime napping behavior, were significant predictors of postpartum mood. CONCLUSIONS The perception of poor sleep, and the conscious awareness of its impact during wake-time, might share a stronger relationship with the occurrence of immediate postpartum mood disturbances than actual sleep quality and quantity.
Making Financial Instability Visible in Space as Well as Time: Towards a more Keynesian Geography

The financial crises of the past decade unfolded at a time when many geographers were already exploring the spatiality of innovative financial structures and globalizing financial markets. The depth and extent of crises raised questions not only about their spatiality, but about their causes and impacts. Geographers were well positioned to discuss the former; but their explorations of these crises’ causes have largely centred on the workings of capitalism as a whole, not on financial processes within capitalism. Hyman Minsky's ‘financial instability hypothesis’, which provides a useful point of departure for understanding the links between financial processes and financial crisis, has been overlooked within economic geography. This chapter explains this lacuna and argues that financial instability should be incorporated into geographic financial discourse. So doing means making analytical space for real time and uncertainty. These elements are at the core of John Maynard Keynes’ ideas, on which Minsky's work builds. Real time and uncertainty are needed if money and credit – and in turn financial instability – are to play an essential analytical role. So bringing financial instability into spatial analysis requires a more Keynesian geography.
Structure Effect of Some New Anticancer Pt(II) Complexes of Amino Acid Derivatives with Small Branched or Linear Hydrocarbon Chains on Their DNA Interaction

The aim of this study was to investigate the structure effect and identify the modes of binding of amino acid‐Pt complexes to DNA molecule for cancer treatment. Hence, three novel water soluble platinum complexes, [Pt(phen)(R‐gly)]NO3 (where phen is 1,10‐phenanthroline, R‐gly is methyl, amyl, and isopentyl‐glycine), have been synthesized and characterized by spectroscopic methods, conductivity measurements, and chemical analysis. The anticancer activities of synthesized complexes were investigated against human breast cancer cell line of MDA‐MB 231. The 50% cytotoxic concentration values were determined to be 42.5, 58, and 70 μm for methyl‐, amyl‐, and isopentyl‐gly complexes, respectively. These complexes were interacted with calf thymus DNA (ct‐DNA) via positive cooperative interaction. The modes of binding of the complexes to DNA were investigated by fluorescence spectroscopy and circular dichroism in combination with a molecular docking study. The result indicates that complexes with small or branched hydrocarbon chains can intercalate with DNA. This is while amyl complexes with linear chains interacted additionally via groove binding. The results of the negative value of Gibbs energy for binding of isopentyl‐platinum to DNA and those of the molecular docking were coherent. Furthermore, the docking results demonstrated that hydrophobic interaction plays an important role in the complex–DNA interaction.