Miracle-dz/UniFAR-FTUs huggingface dataset:
ATP Stimulates Human Macrophages to Kill Intracellular Virulent Mycobacterium tuberculosis Via Calcium-Dependent Phagosome-Lysosome Fusion1

Advances in therapy for tuberculosis will require greater understanding of the molecular mechanisms of pathogenesis and the human immune response in this disease. Exposure of Mycobacterium tuberculosis-infected human macrophages to extracellular ATP (ATPe) results in bacterial killing, but the molecular mechanisms remain incompletely characterized. In this study, we demonstrate that ATPe-induced bactericidal activity toward virulent M. tuberculosis requires an increase in cytosolic Ca2+ in infected macrophages. Based on our previous work with primary infection of human macrophages, we hypothesized that the Ca2+ dependence of ATP-induced killing of intracellular M. tuberculosis was linked to promotion of phagosome-lysosome fusion. Using confocal laser-scanning microscopy, we demonstrate that ATPe induces fusion of the M. tuberculosis-containing phagosome with lysosomes, defined by accumulation of three lysosomal proteins and an acidophilic dye. Stimulation of phagosome-lysosome fusion by ATPe exhibited distinct requirements for both Ca2+ and phospholipase D and was highly correlated with killing of intracellular bacilli. Thus, key signal transduction pathways are conserved between two distinct models of human macrophage antituberculous activity: primary infection of naive macrophages and physiologic stimulation of macrophages stably infected with M. tuberculosis.
An Improved Approach for Estimating Returns to Scale in DEA 1

This article reviews the estimation of Returns To Scale (RTS) in Data Envelopment Analysis (DEA), presented by Golany and Yu and proposes a new method to do this estimation. we show that the new method does not have the shortcoming of the previous one. Furthermore, it is able to evaluate Returns To Scale (RTS) to the right and left of the given unit in all conditions. This method is elaborated by an illustrative example. 2010 Mathematics Subject Classification: 90C05, 65K05, 65K10
Standby-Power-Free Integrated Circuits Using MTJ-Based VLSI Computing

Nonvolatile spintronic devices have potential advantages, such as fast read/write and high endurance together with back-end-of-the-line compatibility, which offers the possibility of constructing not only stand-alone RAMs and embedded RAMs that can be used in conventional VLSI circuits and systems but also standby-power-free high-performance nonvolatile CMOS logic employing logic-in-memory architecture. The advantages of employing spintronic devices, especially magnetic tunnel junction (MTJ) devices with CMOS circuits, are discussed, and the current status of the MTJ-based VLSI computing paradigm is presented along with its prospects and remaining challenges.
BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis

The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. The novel bi-aryl urea BAY 43-9006 is a potent inhibitor of Raf-1, a member of the RAF/MEK/ERK signaling pathway. Additional characterization showed that BAY 43-9006 suppresses both wild-type and V599E mutant BRAF activity in vitro. In addition, BAY 43-9006 demonstrated significant activity against several receptor tyrosine kinases involved in neovascularization and tumor progression, including vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor β, Flt-3, and c-KIT. In cellular mechanistic assays, BAY 43-9006 demonstrated inhibition of the mitogen-activated protein kinase pathway in colon, pancreatic, and breast tumor cell lines expressing mutant KRAS or wild-type or mutant BRAF, whereas non–small-cell lung cancer cell lines expressing mutant KRAS were insensitive to inhibition of the mitogen-activated protein kinase pathway by BAY 43-9006. Potent inhibition of VEGFR-2, platelet-derived growth factor receptor β, and VEGFR-3 cellular receptor autophosphorylation was also observed for BAY 43-9006. Once daily oral dosing of BAY 43-9006 demonstrated broad-spectrum antitumor activity in colon, breast, and non–small-cell lung cancer xenograft models. Immunohistochemistry demonstrated a close association between inhibition of tumor growth and inhibition of the extracellular signal-regulated kinases (ERKs) 1/2 phosphorylation in two of three xenograft models examined, consistent with inhibition of the RAF/MEK/ERK pathway in some but not all models. Additional analyses of microvessel density and microvessel area in the same tumor sections using antimurine CD31 antibodies demonstrated significant inhibition of neovascularization in all three of the xenograft models. These data demonstrate that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis.
Sepsis-Induced Cardiomyopathy: Oxidative Implications in the Initiation and Resolution of the Damage

Cardiac dysfunction may complicate the course of severe sepsis and septic shock with significant implications for patient's survival. The basic pathophysiologic mechanisms leading to septic cardiomyopathy have not been fully clarified until now. Disease-specific treatment is lacking, and care is still based on supportive modalities. Septic state causes destruction of redox balance in many cell types, cardiomyocytes included. The production of reactive oxygen and nitrogen species is increased, and natural antioxidant systems fail to counterbalance the overwhelming generation of free radicals. Reactive species interfere with many basic cell functions, mainly through destruction of protein, lipid, and nucleic acid integrity, compromising enzyme function, mitochondrial structure and performance, and intracellular signaling, all leading to cardiac contractile failure. Takotsubo cardiomyopathy may result from oxidative imbalance. This review will address the multiple aspects of cardiomyocyte bioenergetic failure in sepsis and discuss potential therapeutic interventions.
Time-Series Analysis of Suicidal and Undetermined Deaths

The suicide rate and the death rate for undetermined causes were negatively associated over time from 1968 to 1990 in the USA, suggesting that these undetermined deaths may include a fair proportion of suicides. In contrast, there was no association between suicide and undetermined death rates over the states in 1980.
Perfluorooctane sulphonate and perfluorooctanoic acid in drinking and environmental waters

Perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) are chemicals that have been used for many years as surfactants in a variety of industrial and consumer products. Owing to their persistent, bioaccumulative and toxic (PBT) characteristics, PFOS has been phased out by its principal producer and the use of PFOA has been reduced. This PBT potential and a number of pollution incidents have led in recent years to an increase in studies surveying the concentrations of PFOS and PFOA in environmental waters worldwide. This paper reviews the results of these studies, as well as the monitoring that was conducted after the pollution incidents. The results of surveys suggest that PFOS and PFOA are found in environmental waters worldwide at low levels. In general, these levels are below health-based values set by international authoritative bodies for drinking water. There have been limited measurements of these chemicals in drinking water, but again these are below health-based values, except in some cases following pollution incidents. Monitoring studies suggested that where PFOS and PFOA were detected, they were at similar levels in both source and drinking water, suggesting that drinking water treatment does not remove these chemicals. However, new data show that PFOS and PFOA are effectively removed by granular activated carbon absorbers in practice. Further research is required on the newer perfluorinated chemicals that appear to be safer, but their degradation products have not as yet been fully studied.
X-ray Point Sources in the Sombrero Galaxy: Supersoft Sources, the Globular Cluster/lmxb Connection, and an Overview

We report on the population of point sources discovered during an 18.5 ksec Chandra ACIS-S observation of the Sombrero Galaxy. We present the luminosity function, the spectra of the 6 brightest sources, consider correlations with globular clusters (GCs) and with planetary nebulae (PNe), and study the galaxy's population of SSSs. We detected 122 sources, 22 of them are identified as luminous supersoft X-ray sources (SSSs). There is an over density of SSSs within 1.5 kpc of the nucleus, which is itself the brightest X-ray source. SSSs are also found in the disk and halo, with one SSS in a globular cluster (GC). This source is somewhat harder than most SSSs; the energy distribution of its photons is consistent with what is expected from an accreting intermediate mass black hole. Several sources in Sombrero's halo are good candidates for SSS models in which the accretor is a nuclear-burning white dwarf. In total, 32 X-ray sources are associated with GCs. The majority of sources with luminosity > 10 38 erg s −1 are in GCs. These results for M104, an Sa galaxy, are similar to what has been found for elliptical galaxies and for the late-type spiral M31. We find that those optically bright GCs with X-ray sources house only the brightest X-ray sources. We find that, in common with other galaxies, there appears to be a positive connection between young (metal-rich) GCs and X-ray sources, but that the brightest X-ray sources are equally likely to be in metal-poor GCs. The luminosity function of X-ray sources in GCs has a cut-of near the Eddington luminosity for a 1.4 M ⊙ object. We propose a model which can explain the trends seen in the data sets from the Sombrero and other galaxies. Thermal-time scale mass transfer can occur in some of the the younger clusters in which the turn-off mass is slightly greater than 0.8 M ⊙ ; multiplicity may play a role in some of the most massive clusters; accretion from giant stars may be the dominant mechanism in some older, less massive and less centrally concentrated clusters. Key elements of the model can be tested.
The actin‐bundling protein L‐plastin supports T‐cell motility and activation

Tight regulation of actin dynamics is essential for T‐cell trafficking and activation. Recent studies in human and murine T cells reveal that T‐cell motility and full T‐cell activation require the hematopoietic‐specific, actin‐bundling protein L‐plastin (LPL). T cells lacking LPL do not form fully mature synapses and thus demonstrate reduced cytokine production and proliferation. Reduction or loss of LPL expression also reduces the velocity of T cells and impairs thymic egress and intranodal motility. Whereas dispensable for proximal T‐cell receptor and chemokine receptor signaling, LPL is critical to the later stages of synapse maturation and cellular polarization. Serine phosphorylation, calcium, and calmodulin binding regulate the bundling activity and localization of LPL following T‐cell receptor and chemokine receptor engagement. However, the interaction between these regulatory domains and resulting changes in local control of actin cytoskeletal structures has not been fully elucidated. Circumstantial evidence suggests a function for LPL in either the formation or maintenance of integrin‐associated adhesion structures. As LPL may be a target of the commonly used immunosuppressive agent dexamethasone, full elucidation of the regulation and function of LPL in T‐cell biology may illuminate new pathways for clinically useful immunotherapeutics.
Efficient Private Empirical Risk Minimization for High-dimensional Learning

Dimensionality reduction is a popular approach for dealing with high dimensional data that leads to substantial computational savings. Random projections are a simple and effective method for universal dimensionality reduction with rigorous theoretical guarantees. In this paper, we theoretically study the problem of differentially private empirical risk minimization in the projected subspace (compressed domain). We ask: is it possible to design differentially private algorithms with small excess risk given access to only projected data? In this paper, we answer this question in affirmative, by showing that for the class of generalized linear functions, given only the projected data and the projection matrix, we can obtain excess risk bounds of O(w(C)2/3/n1/3) under e-differential privacy, and O(√w(C)/n) under (eδ)-differential privacy, where n is the sample size and w(C) is the Gaussian width of the parameter space C that we optimize over. A simple consequence of these results is that, for a large class of ERM problems, in the traditional setting (i.e., with access to the original data), under e-differential privacy, we improve the worst-case risk bounds of (Bassily et al., 2014).
Spherical billboards and their application to rendering explosions

This paper proposes an improved billboard rendering method that splats particles as aligned quadrilaterals similarly to previous techniques, but takes into account the spherical geometry of the particles during fragment processing. The new method can eliminate billboard clipping and popping artifacts of previous techniques, happening when the participating medium contains objects, or the camera flies into the volume. This paper also discusses how to use spherical billboards to render high detail explosions made of fire and smoke at high frame rates.
Loneliness in Childhood and Adolescence: Adolescent Loneliness, Self-Reflection, and Identity: From Individual Differences to Developmental Processes

The present chapter focuses on adolescence and illustrates some of the developments that have taken place in research on loneliness during the past few years. Historically, much of the previous research in this area takes the view that loneliness is a sad predicament that is primarily experienced by selected groups of children, such as rejected children (see Asher et al., 1990, for a review) or the learning disabled (Margalit, 1994). Poor relationships with peers are thought to be at the heart of the problem in both cases. The present chapter joins with other chapters in this volume and reflects a growing awareness that loneliness is experienced to a certain degree by everyone (e.g., Hymel, Tarulli, Hayden Thomson, & Terrell-Deutsch, this volume) and that these feelings of relational dissatisfaction are intimately related to various positive developmental changes that take place during adolescence in particular (Larson, this volume). In line with recent developments in the domain, the present chapter also makes a sharp distinction between loneliness on the one hand and aloneness or solitude (i.e., the state of being alone) on the other. Several authors (Cassidy & Asher, 1992; Hymel et al., this volume; Youngblade, Berlin, & Belsky, this volume) have demonstrated that children and adolescents can and do distinguish between these two constructs. On the basis of these findings, an awareness that being alone does not necessarily imply loneliness is currently viewed as a necessary component of a true understanding of what loneliness is. In the present chapter, however, we take this line of reasoning one step further and suggest that individuals' attitude toward being alone be measured in addition to their feelings of loneliness.
Developing a NovaGenesis architecture model for service oriented future Internet and IoT: An advanced transportation system scenario

We are designing a NovaGenesis Architecture Model to support Future Internet services, which are going to address some fundamental issues of the Internet of Things, such as address resolution, mobility, routing, scalability, security, and network control. The aim is to support trillion of things connect to the Internet. In NovaGenesis, we have presented a set of distributed systems where any information processing is seen as service. Services organize themselves based on names and agreements to meet semantics rich goals, policies, regulations, etc. Even networking functionalities are considered as services. Every existence could have one or more names: natural language names or self-certifying names. All the communication, processing, and storage are name-oriented. The protocol stacks are built on demand in a contract-based way. Hence, we can state that NovaGenesis architecture could be an alternative solution for current internet oriented innovations in a scalable manner. The aim of this architecture is the coverage of Internet and sensors oriented smart objects. The paper discusses the proposed model in the context of an Advanced Rural Transportation System.
The university in post-apartheid South Africa : new ethos and new divisions

Higher education in South Africa witnessed significant changes in the 1990s. Some of these changes are a consequence of post-apartheid legislation; others the consequence of global and local changes in the economy. This article argues that many policy goals have not been achieved. This is particularly true of those related to redressing inequities. So, while South African higher education has de-racialised significantly, the less regulated "market" atmosphere of post-apartheid South Africa has widened the divisions between historically privileged and historically black universities. This isn't surprising: institutions with cultural and economic capital will navigate change better than those who lack these. The interesting phenomenon is the fact that English and Afrikaans-language universities are developing in distinctly different directions. While all higher education institutions have, to some extent, been affected by the utilitarianism that currently pervades educational thinking, English universities have engaged with this warily while Afrikaans universities have embraced it. Consequently a new higher education configuration is emerging: . English universities seem to be setting themselves up as slightly modernised versions of the old elite academy; . Afrikaans universities and a rapidly growing private sector represent a new class of entrepreneurial universities, committed to professional qualifications and flexible forms of delivery; . Black niversities are increasingly invisible as educational institutions but far too visible as political trouble spots; at best they may play a "liberal arts college" role in the future but are more likely to be closed down.
SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype

Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. This study shows that SOX11 mRNA and nuclear protein expression is a highly specific marker for both cyclin D1-positive and negative mantle cell lymphoma. See related perspective article on page 1488. Background Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors. Design and Methods The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin D1-negative mantle cell lymphoma, 54 cases of conventional mantle cell lymphoma, and 209 additional lymphoid neoplasms. Results SOX11 mRNA was highly expressed in conventional and cyclin D1-negative mantle cell lymphoma and in 33% of the cases of Burkitt’s lymphoma but not in any other mature lymphoid neoplasm. SOX11 nuclear protein was detected in 50 cases (93%) of conventional mantle cell lymphoma and also in the 12 cyclin D1-negative cases of mantle cell lymphoma, the six cases of lymphoblastic lymphomas, in two of eight cases of Burkitt’s lymphoma, and in two of three T-prolymphocytic leukemias but was negative in the remaining lymphoid neoplasms. Cyclin D2 and D3 mRNA levels were significantly higher in cyclin D1-negative mantle cell lymphoma than in conventional mantle cell lymphoma but the protein expression was not discriminative. The clinico-pathological features and outcomes of the patients with cyclin D1-negative mantle cell lymphoma identified by SOX11 expression were similar to those of patients with conventional mantle cell lymphoma. Conclusions SOX11 mRNA and nuclear protein expression is a highly specific marker for both cyclin D1-positive and negative mantle cell lymphoma.
Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor

Neural cell adhesion molecule (NCAM) mediates cell-cell adhesion and signaling in the nervous system, yet NCAM is also expressed in non-neural tissues, in which its function has in most parts remained elusive. We have previously reported that NCAM stimulates cell-matrix adhesion and neurite outgrowth by activating fibroblast growth factor receptor (FGFR) signaling. Here, we investigated whether the interplay between NCAM and FGFR has any impact on the response of FGFR to its classical ligands, FGFs. To this end, we employed two fibroblast cell lines, NCAM-negative L cells and NCAM-positive NIH-3T3 cells, in which the expression of NCAM was manipulated by means of transfection or RNAi technologies, respectively. The results demonstrate that NCAM expression reduces FGF-stimulated ERK1/2 activation, cell proliferation and cell-matrix adhesion, in both L and NIH-3T3 cells. Furthermore, our data show that NCAM inhibits the binding of FGF to its high-affinity receptor in a competitive manner, providing the mechanisms for the NCAM-mediated suppression of FGF function. In this context, a small peptide that mimics the binding of NCAM to FGFR was sufficient to block FGF-dependent cell proliferation. These findings point to NCAM as being a major regulator of FGF-FGFR interaction, thus introducing a novel type of control mechanism for FGFR activity and opening new therapeutic perspectives for those diseases characterized by aberrant FGFR function.
The Role of Trust and Security Mechanisms in an Agent-Based Peer Help System

In this paper, we hope to document the use of various agent-based trust and security mechanisms in a simulated economic environment that is used to efficiently locate human helpers in a distributed peerhelp environment. The agents and/or mechanisms will be responsible for ensuring that fraudulent or valueless transactions are monitored, and, if possible, the victim compensated. A variety of methods will be used further to this end, including: reference/review agents, police agents and relationship networks. The use of such agents or techniques will also be relevant to similar systems in the area of electronic-commerce or other agent-based applications.