Miracle-dz/UniFAR-FTUs huggingface dataset:
A Decomposition Based Proof for Fast Mixing of a Markov Chain over Balanced Realizations of a Joint Degree Matrix

A joint degree matrix (JDM) specifies the number of connections between nodes of given degrees in a graph, for all degree pairs and uniquely determines the degree sequence of the graph. We consider the space of all balanced realizations of an arbitrary JDM, realizations in which the links between any two degree groups are placed as uniformly as possible. We prove that a swap Markov Chain Monte Carlo (MCMC) algorithm in the space of all balanced realizations of an {\em arbitrary} graphical JDM mixes rapidly, i.e., the relaxation time of the chain is bounded from above by a polynomial in the number of nodes $n$. To prove fast mixing, we first prove a general factorization theorem similar to the Martin-Randall method for disjoint decompositions (partitions). This theorem can be used to bound from below the spectral gap with the help of fast mixing subchains within every partition and a bound on an auxiliary Markov chain between the partitions. Our proof of the general factorization theorem is direct and uses conductance based methods (Cheeger inequality).
Healthy Human T-Cell Responses to Aspergillus fumigatus Antigens

Background Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (TH1–TH17) and destructive allergic (TH2) immunity. How Aspergillus allergens (Asp f proteins) participate in the development of allergic sensitization is unknown. Methodology/Principal Findings To determine whether Asp f proteins are strictly associated with TH2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-γ, IL-4 or IL-17) to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-γ more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 TH1-responses to Asp f3 (a putative peroxismal membrane protein), Asp f9/16 (cell wall glucanase), Asp f11 (cyclophilin type peptidyl-prolyl isomerase) and Asp f22 (enolase). Strong IFN-γ responses were reproduced in most subjects tested over 6 month intervals. Conclusions Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.
Interaction of Colicins with Bacterial Cells I. Studies with Radioactive Colicins

Maeda, Akio (Department of Genetics, University of Wisconsin, Madison), and Masayasu Nomura. Interaction of colicins with bacterial cells. I. Studies with radioactive colicins. J. Bacteriol. 91:685–694. 1966. —By use of a preparation of radioactive colicin E2, the following conclusions, which had been obtained previously from indirect experiments, were tested directly: (i) colicin stays at the receptor site on the cell and acts from there; (ii) colicins E2 and E3 share the same receptor, although their mode of action is entirely different; (iii) colicinogenic cells adsorb homologous colicin, although they are resistant to that colicin. Our experimental results confirmed the above conclusions. When sensitive cells of Escherichia coli K-12 pretreated with radioactive E2 were disrupted with a French pressure cell, and fractionated by differential centrifugation, it was found that most of the radioactivity stayed with the cell envelope fraction. Trypsin removed a major part of radioactivity from cells pretreated with radioactive E2, as was expected from the previous experiments on trypsin reversal of colicin action. Furthermore, it was shown that the trypsin treatment causes a recovery of the capacity of E2-pretreated cells to adsorb further colicin E2. When cells were first treated with various amounts of nonradioactive E3, and then treated with radioactive E2, the amount of radioactive E2 adsorbed was found to be inversely related to the amount of nonradioactive E3 adsorbed first. It was also shown that E2-colicinogenic cells adsorb radioactive E2, and yet are resistant to this colicin.
Expensive Egos: Narcissistic Males Have Higher Cortisol

Background Narcissism is characterized by grandiosity, low empathy, and entitlement. There has been limited research regarding the hormonal correlates of narcissism, despite the potential health implications. This study examined the role of participant narcissism and sex on basal cortisol concentrations in an undergraduate population. Methods and Findings Participants were 106 undergraduate students (79 females, 27 males, mean age 20.1 years) from one Midwestern and one Southwestern American university. Narcissism was assessed using the Narcissistic Personality Inventory, and basal cortisol concentrations were collected from saliva samples in a laboratory setting. Regression analyses examined the effect of narcissism and sex on cortisol (log). There were no sex differences in basal cortisol, F(1,97) = . 20, p = . 65, and narcissism scores, F(1,97) = . 00, p = . 99. Stepwise linear regression models of sex and narcissism and their interaction predicting cortisol concentrations showed no main effects when including covariates, but a significant interaction, β = . 27, p = . 04. Narcissism was not related to cortisol in females, but significantly predicted cortisol in males. Examining the effect of unhealthy versus healthy narcissism on cortisol found that unhealthy narcissism was marginally related to cortisol in females, β = . 27, p = . 06, but significantly predicted higher basal cortisol in males, β = . 72, p = . 01, even when controlling for potential confounds. No relationship was found between sex, narcissism, or their interaction on self-reported stress. Conclusions Our findings suggest that the HPA axis is chronically activated in males with unhealthy narcissism. This constant activation of the HPA axis may have important health implications.
Interfacial cracking in a graded coating/substrate system loaded by a frictional sliding flat punch

An analysis of a coupled plane elasticity problem of crack/contact mechanics for a coating/substrate system with functionally graded properties is performed, where the rigid flat punch slides over the surface of the coated system that contains a crack. The graded material is treated as a non-homogeneous interlayer between dissimilar, homogeneous phases of the coated medium and the crack is assumed to exist along the interface between the interlayer and the substrate. Based on the Fourier integral transform method and the transfer matrix approach, formulation of the current coupled mixed boundary value problem lends itself to the derivation of a set of three simultaneous Cauchy-type singular integral equations. In the numerical results, the emphasis is placed on the investigation of interactions between the contact stress field and the crack-tip behaviour for various combinations of material, geometric and loading parameters of the coated system. Specifically, effects of interfacial cracking on the distributions of the contact pressure and the in-plane stress component along the coating surface are examined and the mixed-mode stress intensity factors evaluated from the crack-tip stress field with the square-root singularity are provided as a function of punch location. Further addressed is the quantification of the singular character of contact pressure distributions at the trailing and leading edges of the flat punch in terms of the punch-edge stress intensity factors. Implicit in this particular analysis of the coupled crack/contact problem presented henceforth is that the crack closure behaviour under the compressive contact stress field is not taken into account, ignoring the influence of crack-face contact and friction.
Environmental Research and Public Health Strongyloidiasis: a Disease of Socioeconomic Disadvantage

Strongyloidiasis is a disease caused by soil transmitted helminths of the Strongyloides genus. Currently, it is predominately described as a neglected tropical disease. However, this description is misleading as it focuses on the geographical location of the disease and not the primary consideration, which is the socioeconomic conditions and poor infrastructure found within endemic regions. This classification may result in misdiagnosis and mistreatment by physicians, but more importantly, it influences how the disease is fundamentally viewed. Strongyloidiasis must be first and foremost considered as a disease of disadvantage, to ensure the correct strategies and control measures are used to prevent infection. Changing how strongyloidiasis is perceived from a geographic and clinical issue to an environmental health issue represents the first step in identifying appropriate long term control measures. This includes emphasis on environmental health controls, such as better infrastructure, sanitation and living conditions. This review explores the global prevalence of strongyloidiasis in relation to its presence in subtropical, tropical and temperate climate zones with mild and cold winters, but also explores the corresponding socioeconomic conditions of these regions. The evidence shows that strongyloidiasis is primarily determined by the socioeconomic status of the communities rather than geographic or climatic conditions. It demonstrates that strongyloidiasis should no longer be referred to as a " tropical " disease but rather a disease of disadvantage. This philosophical shift will promote the development of correct control strategies for preventing this disease of disadvantage.
TRPM7 Is Essential for RANKL-Induced Osteoclastogenesis

The transient receptor potential melastatin type 7 (TRPM7) channel is a widely expressed non-selective cation channel with fusion to the C-terminal alpha kinase domain and regarded as a key regulator of whole body Mg2+ homeostasis in mammals. However, the roles of TRPM7 during osteoclastogenesis in RAW264.7 cells and bone marrow-derived monocyte/macrophage precursor cells (BMMs) are not clear. In the present study, we investigate the roles of TRPM7 in osteoclastogenesis using methods of small interfering RNA (siRNA), RT-PCR, patch-clamp, and calcium imaging. RANKL (receptor activator of NF-κB ligand) stimulation did not affect the TRPM7 expression and TRPM7-mediated current was activated in HEK293, RAW264.7, and BMM cells by the regulation of Mg2+. Knock-down of TRPM7 by siTRPM7 reduced intracellular Ca2+ concentration ([Ca2+]i) increases by 0 mM [Mg2+]e in HEK293 cells and inhibited the generation of RANKL-induced Ca2+ oscillations in RAW264.7 cells. Finally, knock-down of TRPM7 suppressed RANKL-mediated osteoclastogenesis such as activation and translocation of NFATc1, formation of multinucleated cells, and the bone resorptive activity, sequentially. These results suggest that TRPM7 plays an essential role in the RANKL-induced [Ca2+]i oscillations that triggers the late stages of osteoclastogenesis.
Novel Piperazine-based Compounds Inhibit Microtubule Dynamics and Sensitize Colon Cancer Cells to Tumor Necrosis Factor-induced Apoptosis*

Background: Mitotic spindles are important targets of cancer chemotherapeutic agents. Results: A new class of tubulin-targeting agents is identified that effectively sensitizes colon cancer cells to ligand-induced apoptosis. Conclusion: AK301 is a novel, piperazine-based compound that induces mitotic arrest and increases ligand-dependent apoptosis. Significance: Mitotically active compounds that stimulate ligand-induced apoptotic signaling might be useful for augmenting immune-based cancer therapies. We recently identified a series of mitotically acting piperazine-based compounds that potently increase the sensitivity of colon cancer cells to apoptotic ligands. Here we describe a structure-activity relationship study on this compound class and identify a highly active derivative ((4-(3-chlorophenyl)piperazin-1-yl)(2-ethoxyphenyl)methanone), referred to as AK301, the activity of which is governed by the positioning of functional groups on the phenyl and benzoyl rings. AK301 induced mitotic arrest in HT29 human colon cancer cells with an ED50 of ≈115 nm. Although AK301 inhibited growth of normal lung fibroblast cells, mitotic arrest was more pronounced in the colon cancer cells (50% versus 10%). Cells arrested by AK301 showed the formation of multiple microtubule organizing centers with Aurora kinase A and γ-tubulin. Employing in vitro and in vivo assays, tubulin polymerization was found to be slowed (but not abolished) by AK301. In silico molecular docking suggests that AK301 binds to the colchicine-binding domain on β-tubulin, but in a novel orientation. Cells arrested by AK301 expressed elevated levels of TNFR1 on their surface and more readily activated caspases-8, -9, and -3 in the presence of TNF. Relative to other microtubule destabilizers, AK301 was the most active TNF-sensitizing agent and also stimulated Fas- and TRAIL-induced apoptosis. In summary, we report a new class of mitosis-targeting agents that effectively sensitizes cancer cells to apoptotic ligands. These compounds should help illuminate the role of microtubules in regulating apoptotic ligand sensitivity and may ultimately be useful for developing agents that augment the anti-cancer activities of the immune response.
Fabrication of 1D, 2D and 3D polymer-based periodic structures by mass transport effect

We have theoretically and experimentally investigated the formation of both active and passive surface relief gratings on two kinds of photosensitive polymers: negative photoresist and azobenzene copolymer. The common mechanism of the structures formation was attributed to mass transport effect, which however pushes the materials in opposite directions in these two materials. The fabrication technique is based on the use of interference lithography, which allowed to create large and uniform structures. In the first case, 1D and 2D passive periodic surface relief structures were created on the negative photoresist SU8 thanks to the shrinkage effect during the crosslinking process. In the second case, 1D, 2D and 3D active periodic structures have been obtained thanks to the movement of DR1/PMMA copolymer materials from regions of high intensity to those of low intensity irradiation. The modulation amplitude of structures is optimized by controlling the film thickness, the structure periodicity, the exposure dosage, and the polarizations of interference laser beams. Applications of these structures for multiple wavelength DFB laser, nonlinear photonic crystals, and waveguide coupling have been discussed.
Signal transduction from the extracellular matrix

Adhesive interactions between cells and the insoluble meshwork of extracellular matrix proteins play a vital role in embryonic morphogenesis (33, 36, 94, 109, 135, 145), and in the regulation of gene expression in cells of the adult organism (1, 6, 105, 124). While the overall phenomenology ofextracellular matrix (ECM) 1 effects on cell differentiation is well known, the biochemical and molecular bases for these effects have remained elusive. It is clear that many of the interactions between cells and the ECM are mediated by the integrin family of cell surface receptors (2, 3, 13, 72). However, the precise mechanism(s) whereby signals from ECM proteins are transduced via integfins to the intraceUular machinery that controls cell growth, behavior, and differentiation, remains poorly defined. There are many compelling examples of control of cell differentiation and gene expression through adhesive interactions with extracellular matrix. In fibroblasts, cell attachment has been reported to rapidly increase expression of c-los and pro al(I) collagen messages (26, 27). Adhesion to fibronectin fragments, or cross-linking of the integfin oe5/~l fibronectin receptor with antibody, induced the expression of metalloprotease genes in fibroblastic cells; interestingly, intact fibronectin did not provoke this response nor did fibronectin fragments in solution (137). In a somewhat similar vein, stimulation of the C~v//~3 integrin in melanoma cells induced the expression of type IV collagenase and increased the invasive ability of these cells (115). The capacity of breast epithelial cells to express milk proteins in response to hormonal stimuli is quite dependent on the presence of an appropriate ECM (124). Studies in this system have led to the preliminary identification of matrix-dependent elements in the promoter region of the ~ casein gene (111). In the immune system, activation of T-lymphocytes through the T-cell antigen receptor is markedly enhanced by integrin-mediated adhesion to fibronectin or laminin (85, 97, 119). This process is part of a complex dialogue involving adhesive receptors occurring between mature T-cells and antigen presenting cells, as well as during lymphocyte differentiation (40, 132, 133). There is extensive signaling "cross talk" between
The KIDS SAFE checklist for pediatric intensive care units.

BACKGROUND Checklists have been recognized by multiple industries as a valuable tool to reduce errors of omission. In the busy environment of a pediatric intensive care unit, adverse events are common and can have severe consequences. Researchers have focused on developing evidence-based practice guidelines; however, the nature of human error means that consistent application of this evidence in practice is challenging. OBJECTIVE To develop an evidence-based checklist as a tool to reduce preventable adverse events and enhance clinical care in pediatric intensive care units. METHODS After a systematic review of literature and a retrospective review of local reporting of adverse events in pediatric intensive care units, nominal group technique was used to determine the structure and content for the checklist. RESULTS An 8-element mnemonic checklist (KIDS SAFE) was developed: kids' development needs, infection, deep-vein thrombosis prophylaxis, skin integrity, sedation, analgesia, family, and enteral needs. CONCLUSION Prevention of adverse events is better than cure. Use of the KIDS SAFE checklist has the potential to reduce errors of omission in pediatric intensive care units.
The Host Environment Is Responsible for Aging-Related Functional NK Cell Deficiency

NK cells play an important role in immunity against infection and tumors. Aging-related functional NK cell deficiency is well documented in humans and mice. However, the mechanism for this is poorly understood. Using an adoptive transfer approach in mice, we found that NK cells from both young and aged mice responded vigorously to priming by pathogen-derived products after being cotransferred into young mice. In contrast, NK cells from young mice responded poorly to priming by pathogen-derived products after being transferred to aged mice. In addition to defects in NK cell priming, maturation of NK cells under steady-state conditions is also impaired in aged mice, resulting in a decreased proportion of CD27− mature NK cells. We found that bone marrow from young and aged mice gave rise to CD27− mature NK cells similarly in young mixed bone marrow chimeric mice. Furthermore, by using a novel bone marrow transfer approach without irradiation, we found that after being transferred to aged mice, bone marrow from young mice gave rise to NK cells with maturation defects. Finally, we found that aging-related functional NK cell deficiency was completely reversed by injecting soluble IL-15/IL-15Rα complexes. In contrast, blockade of IL-10 signaling, which broadly augments inflammatory responses to pathogen-derived products, had little effect on aging-related defects in NK cell priming. These data demonstrate that the aged host environment is responsible for aging-related functional NK cell deficiency. Additionally, our data suggest that IL-15 receptor agonists may be useful tools in treating aging-related functional NK cell deficiency.
Percutaneous ablation for hepatocellular carcinoma

We read with interest the paper by Di Martino et al. published in the December 2004 issue of HEPATOLOGY1 that examines estrogen-related effects on hepatitis C fibrosis. Specifically, progression of hepatitis C fibrosis was correlated with prior pregnancies, menopausal status, past use of oral contraceptives, and hormone replacement therapy. Hepatitis C–infected women who completed a survey and had previously undergone liver biopsy were eligible for the study. The investigators calculated a rate of progression of fibrosis, dividing fibrosis stage (in Metavir units) by years of hepatitis C infection. This approach has been used previously in a selfdescribed cross-sectional study.2 The present study is labeled a “retrospective cohort study,” although it would be better characterized as a cross-sectional study. Information from a single survey was correlated with results from a single liver biopsy. Patients were not followed by repeated biopsies or repeated surveys over time. The distinction between cohort and cross-sectional is not merely semantic in this case. Figures 3 and 4 are Kaplan-Meier curves for the development of significant fibrosis in “cohorts” of hepatitis C patients. Kaplan-Meier curves depend on the precise knowledge of when a patient in a cohort develops significant fibrosis. For example, a patient with a biopsy showing stage 4 fibrosis and 20 years of disease duration would be plotted on a Kaplan-Meier curve as having developed significant fibrosis (stage 2) after 20 years’ disease duration. Without a prior biopsy, it is not known at what time the patient actually developed stage 2 fibrosis. To address the impossibility of accurate censoring, the authors could have back-extrapolated to estimate time to development of stage 2 fibrosis, assuming linear progression of fibrosis. The problem with that approach is that it involves using a calculated result to generate primary data—for re-analysis. In short, even though the investigators describe a rate of progression of fibrosis, the data do not truly describe a cohort. Statistical methods generally reserved for cohort studies cannot be applied easily to cross-sectional data.