Miracle-dz/UniFAR-FTUs huggingface dataset:
Preservation of Metabolic Flexibility in Skeletal Muscle by a Combined Use of n-3 PUFA and Rosiglitazone in Dietary Obese Mice

Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil–based high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients.
Younger Age Is Associated with Poorer Survival in Patients with Signet-Ring Cell Carcinoma of the Colon without Distant Metastasis

Background. In general, younger age is associated with better survival in patients with colon cancer. In this study, we aim to analyze the impact of age on cancer-specific survival (CSS) in patients with signet-ring cell carcinoma (SRCC) of the colon, a particularly aggressive type of colon cancer. Methods. Information on patients with SRCC of the colon with no distant metastasis was extracted from the US Surveillance, Epidemiology, and End Results (SEER) database. An X-tile plot was used to determine the optimal cutoff age at diagnosis. Results. A total of 776 patients were included in data analysis. The X-tile program revealed an optimal cutoff at 35 years of age. A higher percentage of stage III disease and a higher percentage of N2 disease were observed in patients ≤ 35 years of age. The multivariate Cox proportional model demonstrated that patients ≤ 35 years of age were more likely to have a poorer survival outcome compared with patients aged >35 years (HR 1.411, 95% CI 1.032–1.929, and P = 0.031). Conclusion. In contrast to the association of younger age with better survival in colon cancer patients, younger age (≤35 years) is associated with poorer survival outcome in patients with SRCC of the colon without distant metastasis.
Latin@s in Science, Technology, Engineering, and Mathematics (STEM) at the Intersections

ABSTRACT As the United States population approaches a minority majority, the need to address educational inequities is intensified, especially for Latin@ students who are among the fastest growing ethnic minority group across the United States and at four-year colleges and universities. Concerns for educational equity also demand broadening participation of domestic under-represented groups in science, technology, engineering, and mathematics (STEM) fields. Informed by student-level data from six large, public, doctoral-granting, research-intensive universities located in the Midwest and Mid-Atlantic regions, we examine differences in STEM degree attainment among Latin@s at the intersections of race/ethnicity, gender, and socioeconomic status. The results support the need to target STEM intervention efforts to Latin@s by gender.
Viscous Stability of Relativistic Keplerian Accretion Disks

We investigate the viscous stability of thin, Keplerian accretion disks in regions in which general relativistic (GR) effects are essential. For gas pressure-dominated (GPD) disks, we show that the Newtonian conclusion that such disks are viscously stable is reversed by GR modifications in the behaviors of viscous stress and surface density over a significantly large annular region not far from the innermost stable orbit at r=rms. For slowly rotating central objects, this region spans a range of radii 14 ≲ r ≲ 19 in units of the central object's mass M. For radiation pressure-dominated (RPD) disks, the Newtonian conclusion that they are viscously unstable remains valid after including the above GR modifications, except in a very small annulus around r ≈ 14 M, which has a negligible influence. Inclusion of the stabilizing effect of the mass inflow through the disk's inner edge via a GR analog of Roche lobe overflow adds a small, stable region around rms for RPD disks but leaves GPD disks unchanged. We mention possible astrophysical relevance of these results, particularly to the high-frequency X-ray variabilities observed by the Rossi X-Ray Timing Explorer.
Melanoma-Derived Wnt5a Promotes Local Dendritic-Cell Expression of IDO and Immunotolerance: Opportunities for Pharmacologic Enhancement of Immunotherapy

Melanomas produce Wnt5a, which promotes the ability of local DCs to drive regulatory T-cell expansion and to generate an immunosuppressive tumor microenvironment. Targeting this system could lead to the development of novel immunotherapeutic strategies. The β-catenin signaling pathway has been demonstrated to promote the development of a tolerogenic dendritic cell (DC) population capable of driving regulatory T-cell (Treg) differentiation. Further studies have implicated tolerogenic DCs in promoting carcinogenesis in preclinical models. The molecular mechanisms underlying the establishment of immune tolerance by this DC population are poorly understood, and the methods by which developing cancers can co-opt this pathway to subvert immune surveillance are currently unknown. This work demonstrates that melanoma-derived Wnt5a ligand upregulates the durable expression and activity of the indoleamine 2,3-dioxygenase-1 (IDO) enzyme by local DCs in a manner that depends upon the β-catenin signaling pathway. These data indicate that Wnt5a-conditioned DCs promote the differentiation of Tregs in an IDO-dependent manner, and that this process serves to suppress melanoma immune surveillance. We further show that the genetic silencing of the PORCN membrane–bound O-acyl transferase, which is necessary for melanoma Wnt ligand secretion, enhances antitumor T-cell immunity, and that the pharmacologic inhibition of this enzyme synergistically suppresses melanoma progression when combined with anti–CTLA-4 antibody therapy. Finally, our data suggest that β-catenin signaling activity, based on a target gene expression profile that includes IDO in human sentinel lymph node–derived DCs, is associated with melanoma disease burden and diminished progression-free survival. This work implicates the Wnt–β-catenin signaling pathway as a novel therapeutic target in the melanoma immune microenvironment and demonstrates the potential impact of manipulating DC function as a strategy for optimizing tumor immunotherapy. Cancer Immunol Res; 3(9); 1082–95. ©2015 AACR.
Stereo vision matching over single-channel color-based segmentation

Stereo vision is one of the most important passive methods to extract depth maps. Among them, there are several approaches with advantages and disadvantages. Computational load is especially important in both the block matching and graphical cues approaches. In a previous work, we proposed a region growing segmentation solution to the matching process. In that work, matching was carried out over statistical descriptors of the image regions, commonly referred to as characteristic vectors, whose number is, by definition, lower than the possible block matching possibilities. This first version was defined for gray scale images. Although efficient, the gray scale algorithm presented some important disadvantages, mostly related to the segmentation process. In this article, we present a pre-processing tool to compute gray scale images that maintains the relevant color information, preserving both the advantages of gray scale segmentation and those of color image processing. The results of this improved algorithm are shown and compared to those obtained by the gray scale segmentation and matching algorithm, demonstrating a significant improvement of the computed depth maps.
ENGLISH LEXICAL STRESS CUES IN NATIVE ENGLISH AND NON-NATIVE ARABIC SPEAKERS

Individuals who speak English as a second language vary in their ability to produce appropriate stress, which often impedes their intelligibility. The present study investigated the production of lexical stress by native speakers of English as well as learners of English. Minimal pairs were recorded by 8 native speakers of English and 8 Arabic learners of English. A second experiment examined use of acoustic cues to indicate stressed syllables in Arabic (8 speakers). In both experiments, four acoustic cues were examined: duration, fundamental frequency, amplitude, and second formant frequency. Differences in the use of these cues were observed across speaker groups (native and non-native speakers) for fundamental frequency and second formant frequency. These differences in use of cues to signal stress were only partially related to use of these acoustic cues in the speakers’ first language.
Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a, a potential anticancer drug

There has been increasing interest in the potential applications of gold (III) complexes as anticancer drugs with higher cytotoxicity and fewer side effects than existing metal anticancer drugs. Our previous findings demonstrated that gold (III) porphyrin 1a preferentially induced apoptosis in a cancer cell line (SUNE1). In this study, we identified differentially expressed proteins related to the drug's cytotoxic action by comparing the protein alterations induced by gold (III) porphyrin 1a and cisplatin treatments. Several clusters of altered proteins were identified, including cellular structure and stress‐related chaperone proteins, proteins involved in reactive oxygen species and enzyme proteins, translation factors, proteins that mediate cell proliferation or differentiation, and proteins participating in the internal degradation systems. Our results indicated that multiple factors leading to apoptosis were involved in drug cytotoxicity in SUNE1 cells. The balance between pro‐apoptotic and anti‐apoptotic signals determined the final fate of cancer cells.
Chlorogenic Acid Stimulates Glucose Transport in Skeletal Muscle via AMPK Activation: A Contributor to the Beneficial Effects of Coffee on Diabetes

Chlorogenic acid (CGA) has been shown to delay intestinal glucose absorption and inhibit gluconeogenesis. Our aim was to investigate the role of CGA in the regulation of glucose transport in skeletal muscle isolated from db/db mice and L6 skeletal muscle cells. Oral glucose tolerance test was performed on db/db mice treated with CGA and soleus muscle was isolated for 2-deoxyglucose transport study. 2DG transport was also examined in L6 myotubes with or without inhibitors such as wortmannin or compound c. AMPK was knocked down with AMPKα1/2 siRNA to study its effect on CGA-stimulated glucose transport. GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA. In db/db mice, a significant decrease in fasting blood sugar was observed 10 minutes after the intraperitoneal administration of 250 mg/kg CGA and the effect persisted for another 30 minutes after the glucose challenge. Besides, CGA stimulated and enhanced both basal and insulin-mediated 2DG transports in soleus muscle. In L6 myotubes, CGA caused a dose- and time-dependent increase in glucose transport. Compound c and AMPKα1/2 siRNA abrogated the CGA-stimulated glucose transport. Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities. CGA did not appear to enhance association of IRS-1 with p85. However, we observed activation of Akt by CGA. These parallel activations in turn increased translocation of GLUT 4 to plasma membrane. At 2 mmol/l, CGA did not cause any significant changes in viability or proliferation of L6 myotubes. Our data demonstrated for the first time that CGA stimulates glucose transport in skeletal muscle via the activation of AMPK. It appears that CGA may contribute to the beneficial effects of coffee on Type 2 diabetes mellitus.
Shaping Earnings Insecurity: Labor Market Policy and Institutional Factors

We examine the relationship between earnings insecurity, labor market policies/institutions, product market regulation, and macroeconomic shocks across Europe in the 1990s by means of the non-linear least squares method. Earnings insecurity is proxied by transitory variability in earnings, which captures transitory earnings shocks, and by earnings volatility, which captures both permanent and transitory earnings shocks. Our results suggest that corporative bargaining systems, generous unemployment benefits, and deregulated product markets reduce the impact of macroeconomic shocks on transitory variability in earnings and earnings volatility, while a stronger labor protection legislation reduces the impact of macroeconomic shocks on earnings volatility. Several institutional mixes have the potential to reduce transitory variability, for example coupling a high corporatism with a high unionization, coupling protection mechanisms with activation policies, incorporating a trade-off between the generosity of unemployment benefits and the strictness of labor market regulation, and coupling product market deregulation with deregulated labor markets or with a high unionization. Two valuable lessons are that contextual interaction effects are important for understanding the influence of particular policies and institutions on earnings insecurity and that there is no one-size-fits all policy package for reducing the impact of the business cycle on transitory variability and volatility.
Interactions of β-Conglycinin (7S) with Different Phenolic Acids—Impact on Structural Characteristics and Proteolytic Degradation of Proteins

p-Coumalic acid (PCA), caffeic acid (CA), gallic acid (GA) and chlorogenic acid (CGA) are the major phenolic acids that co-exist with soy protein components in foodstuffs. Surprisingly, there are only a handful of reports that describe their interaction with β-Conglycinin (7S), a major soy protein. In this report, we investigated the interaction between phenolic acids and soy protein 7S and observed an interaction between each of these phenolic acids and soy protein 7S, which was carried out by binding. Further analysis revealed that the binding activity of the phenolic acids was structure dependent. Here, the binding affinity of CA and GA towards 7S was found to be stronger than that of PCA, because CA and GA have one more hydroxyl group. Interestingly, the binding of phenolic acids with soy protein 7S did not affect protein digestion by pepsin and trypsin. These findings aid our understanding of the relationship between different phenolic acids and proteins in complex food systems.
Parents Without Papers: The Progress and Pitfalls of Mexican American Integration

In Parents Without Papers, immigra on scholars Frank D. Bean and Susan K. Brown document the extent to which the outsider status of these newcomers inflicts mul ple hardships on their children and grandchildren. Parents Without Papers provides both a general conceptualiza on of immigrant integra on and an in‐depth examina on of the Mexican American case. The authors draw upon unique retrospec ve data to shed light on three gen‐ era ons of integra on.
A method for making group inferences from functional MRI data using independent component analysis

Independent component analysis (ICA) is a promising analysis method that is being increasingly applied to fMRI data. A principal advantage of this approach is its applicability to cognitive paradigms for which detailed models of brain activity are not available. Independent component analysis has been successfully utilized to analyze single‐subject fMRI data sets, and an extension of this work would be to provide for group inferences. However, unlike univariate methods (e.g., regression analysis, Kolmogorov–Smirnov statistics), ICA does not naturally generalize to a method suitable for drawing inferences about groups of subjects. We introduce a novel approach for drawing group inferences using ICA of fMRI data, and present its application to a simple visual paradigm that alternately stimulates the left or right visual field. Our group ICA analysis revealed task‐related components in left and right visual cortex, a transiently task‐related component in bilateral occipital/parietal cortex, and a non‐task‐related component in bilateral visual association cortex. We address issues involved in the use of ICA as an fMRI analysis method such as: (1) How many components should be calculated? (2) How are these components to be combined across subjects? (3) How should the final results be thresholded and/or presented? We show that the methodology we present provides answers to these questions and lay out a process for making group inferences from fMRI data using independent component analysis. Hum. Brain Mapping 14:140–151, 2001. © 2001 Wiley‐Liss, Inc.
The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics

Significance Phase transitions have recently emerged as a key mechanism for intracellular organization. However, the underlying molecular interactions and nature of the resulting condensed phases are poorly understood. Here, we identify a role for LAF-1 in the liquid phase separation of P granules—RNA/protein assemblies implicated in germ-line maintenance. We adapt microrheology techniques to measure precise viscoelastic properties of LAF-1 liquid droplets. Our experiments reveal that electrostatic disordered protein interactions give rise to droplets with tunable material properties. RNA can fluidize protein droplets by decreasing the viscosity and increasing internal molecular dynamics. Our results provide insight into the mechanism by which molecular level interactions can give rise to liquid phase organelles with tunable material properties, potentially underlying biologically adaptable functions. P granules and other RNA/protein bodies are membrane-less organelles that may assemble by intracellular phase separation, similar to the condensation of water vapor into droplets. However, the molecular driving forces and the nature of the condensed phases remain poorly understood. Here, we show that the Caenorhabditis elegans protein LAF-1, a DDX3 RNA helicase found in P granules, phase separates into P granule-like droplets in vitro. We adapt a microrheology technique to precisely measure the viscoelasticity of micrometer-sized LAF-1 droplets, revealing purely viscous properties highly tunable by salt and RNA concentration. RNA decreases viscosity and increases molecular dynamics within the droplet. Single molecule FRET assays suggest that this RNA fluidization results from highly dynamic RNA–protein interactions that emerge close to the droplet phase boundary. We demonstrate than an N-terminal, arginine/glycine rich, intrinsically disordered protein (IDP) domain of LAF-1 is necessary and sufficient for both phase separation and RNA–protein interactions. In vivo, RNAi knockdown of LAF-1 results in the dissolution of P granules in the early embryo, with an apparent submicromolar phase boundary comparable to that measured in vitro. Together, these findings demonstrate that LAF-1 is important for promoting P granule assembly and provide insight into the mechanism by which IDP-driven molecular interactions give rise to liquid phase organelles with tunable properties.
Achieving economic and environmental sustainability through optimum balance of costs

Awareness and significance of sustainable development (SD) has been growing around the world for the last few decades. Sustainable construction is now considered a way for the construction industry to contribute to this larger effort. It is clear why the construction industry must respond accordingly and focus its attention on developing more sustainable buildings - not least because of its huge size, the vast amount of resources it consumes and its major impact on the built and natural environments. This research work therefore aims to examine the concept of sustainability, investigate the costs related to producing sustainable buildings and the relationship that exists between these costs. A review of the literature showed that the concept of sustainability is broad but the economic, social and environmental aspects, which are inextricably linked, remain the three fundamental pillars of sustainability. Initial construction cost (IC), cost-in-use (CIU) and carbon cost (CC) were revealed as monetary means of appraising economic and environmental criteria. According to the review, social criteria are drivers: subjective and human factors, which affect the other two factors, directly or indirectly. It is concluded that inverse relationship often exists between IC and CIU but the movement of CC in relation to this is still unknown, being a new concept. Further stage of the research work will explore this grey area and consequently model through quantitative analysis the relationship that exists between IC, CIU and CC.
Normal Bundles of Rational Curves in Projective Spaces

We determine the splitting (isomorphism) type of the normal bundle of a generic genus-0 curve with 1 or 2 components in any projective space, as well as the (sometimes nontrivial) way the bundle deforms locally with a general deformation of the curve. We deduce an enumerative formula for divisorial loci of smooth rational curves whose normal bundle is of non-generic splitting type.
Hierarchical Case-Based Reasoning Integrating Case-Based and Decompositional Problem-Solving Techniques for Plant-Control Software Design

Case based reasoning (CBR) is an artificial intelligence technique that emphasises the role of past experience during future problem solving. New problems are solved by retrieving and adapting the solutions to similar problems, solutions that have been stored and indexed for future reuse as cases in a case-base. The power of CBR is severely curtailed if problem solving is limited to the retrieval and adaptation of a single case, so most CBR systems dealing with complex problem solving tasks have to use multiple cases. The paper describes and evaluates the technique of hierarchical case based reasoning, which allows complex problems to be solved by reusing multiple cases at various levels of abstraction. The technique is described in the context of Deja Vu, a CBR system aimed at automating plant-control software design.