Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-4 Is Required for Sex Differences in Vulnerability to Focal Ischemia in Mice

Background and Purpose— Interleukin (IL)-4 protects from middle cerebral artery occlusion in male mice. Females generally show less injury in response to the same ischemic challenge, but the underlying mechanisms are not fully understood. We tested the importance of IL-4 in female protection using IL-4 knockout (KO) mice. Methods— IL-4 KO and wild-type (WT) mice of both sexes were subjected to middle cerebral artery occlusion. Infarct volume was assessed by triphenyltetrazolium chloride staining and neurobehavioral outcome by neuroscore. T cell proliferation was assessed after Concanavalin A exposure. Ischemic brain immune cell populations were analyzed by fluorescence-activated cell sorting and immunostaining. Results— Infarction in WT females during estrus and proestrus phases was significantly smaller than in males; neurological score was better. Infarction volume was larger and neurological score worse in IL-4 KO compared with WT in both sexes, with no sex difference. Proliferation of T cells was inhibited in WT females with higher proliferation and no sex difference in IL-4 KO. Macrophage numbers and total T cells in the ischemic hemisphere were lower in WT females, and monocytes increased markedly in IL-4 KOs with no sex difference. The reduced macrophage infiltration in WT-females was predominantly M2. Loss of IL-4 increased CD68+ and iNOS+ cells and reduced YM1+ and Arg1+ cells in both sexes. Conclusions— IL-4 is required for female neuroprotection during the estrus phase of the estrus cycle. Protected WT females show a predominance of M2-activated microglia/macrophages and reduced inflammatory infiltration. Increasing macrophage M2 polarization, with or without added inhibition of infiltration, may be a new approach to stroke treatment.
VisLink: Revealing Relationships Amongst Visualizations

We present VisLink, a method by which visualizations and the relationships between them can be interactively explored. VisLink readily generalizes to support multiple visualizations, empowers inter-representational queries, and enables the reuse of the spatial variables, thus supporting efficient information encoding and providing for powerful visualization bridging. Our approach uses multiple 2D layouts, drawing each one in its own plane. These planes can then be placed and re-positioned in 3D space: side by side, in parallel, or in chosen placements that provide favoured views. Relationships, connections, and patterns between visualizations can be revealed and explored using a variety of interaction techniques including spreading activation and search filters.
Sintering process of silver nanoparticles in ink-jet printed conductive microstructures - Molecular dynamics approach

The electronic microstructures performed by ink-jet printing nanosilver-contained inks are nonconductive just after the printing. To obtain good electrical conductivity they require the additional energy, mostly supplied during a heating process in relatively high temperature (above 200°C). Such high temperature is not convenient for the most polymers which would play a role of flexible substrates for circuits performed by ink-jet printing technique. The better understanding of sintering process is required to reduce this temperature to a more acceptable. The deep study on the sintering process of silver nanoparticles seems to be useful for further activities towards the reducing process temperature. Within this paper the sintering process of commercially available ink (AX JP-6n, produced by Amepox Microelectronics Ltd.) were investigated. The activation energy of two stages of sintering process were estimated. The experimental results were complemented with the results obtained within molecular dynamics simulations. The molecular dynamics were used for calculations of electrostatic energy between ligands and silver nanoparticles. The Material Studio from Accelerys software were used. Calculations were performed by using the three dimensional model containing the surface made of silver and one particle of ligand.
New approximation algorithms for minimum enclosing convex shapes

Given <i>n</i> points in a <i>d</i> dimensional Euclidean space, the Minimum Enclosing Ball (MEB) problem is to find the ball with the smallest radius which contains all <i>n</i> points. We give two approximation algorithms for producing an enclosing ball whose radius is at most ε away from the optimum. The first requires <i>O</i>(<i>nd</i>£/√ε) effort, where £ is a constant that depends on the scaling of the data. The second is a <i>O</i>*(<i>nd</i>Q/√ε) approximation algorithm, where Q is an upper bound on the norm of the points. This is in contrast with <i>coresets</i> based algorithms which yield a <i>O</i>(<i>nd</i>/ε) greedy algorithm. Finding the Minimum Enclosing Convex Polytope (MECP) is a related problem wherein a convex polytope of a fixed shape is given and the aim is to find the smallest magnification of the polytope which encloses the given points. For this problem we present <i>O</i>(<i>mnd</i>£/ε) and <i>O</i>* (<i>mnd</i>Q/ε) approximation algorithms, where <i>m</i> is the number of faces of the polytope. Our algorithms borrow heavily from convex duality and recently developed techniques in non-smooth optimization, and are in contrast with existing methods which rely on geometric arguments. In particular, we specialize the excessive gap framework of Nesterov [19] to obtain our results.
Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice*

Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration.
Matrix Completion from Fewer Entries: Spectral Detectability and Rank Estimation

The completion of low rank matrices from few entries is a task with many practical applications. We consider here two aspects of this problem: detectability, i.e. the ability to estimate the rank $r$ reliably from the fewest possible random entries, and performance in achieving small reconstruction error. We propose a spectral algorithm for these two tasks called MaCBetH (for Matrix Completion with the Bethe Hessian). The rank is estimated as the number of negative eigenvalues of the Bethe Hessian matrix, and the corresponding eigenvectors are used as initial condition for the minimization of the discrepancy between the estimated matrix and the revealed entries. We analyze the performance in a random matrix setting using results from the statistical mechanics of the Hopfield neural network, and show in particular that MaCBetH efficiently detects the rank $r$ of a large $n\times m$ matrix from $C(r)r\sqrt{nm}$ entries, where $C(r)$ is a constant close to $1$. We also evaluate the corresponding root-mean-square error empirically and show that MaCBetH compares favorably to other existing approaches.
Dual-Band Pin-Patch Antenna for Wi-Fi Applications

The pin-patch antenna provides a low-profile monopolar element suitable for wireless access point requirements. This design concept is extended here to provide dual-band operation. Experimental results are compared to predictions from a FDTD package confirming monopolar radiation in two bands at 2.4 GHz and 5.7 GHz. This band spacing can be adjusted from 1.8:1 to more than 4:1.
Cu-Cu Bonding Alternative to Solder based Micro-Bumping

High strength Cu-Cu thermo-compression bonds have been obtained at temperatures as low as 210degC. The bonded Cu surfaces were prepared by diamond bit cutting from electroplated structures. The electrical yield of bump chains depends on bonding temperature and bump size. At bonding temperatures of 300degC and over, bumps of 15 and of 20 mum diameter are bonded with high yield. Below 300degC, the yield decreases strongly for the larger bumps. However, chains made up of 15 mum bumps show high yield when bonded at 250 or 230degC, and still show 70% yield when bonded at 210degC. The electrical resistance of the bonded interface was too small to be determined separately. In shear testing, failure of the bumps does not occur at the bonded interface but after strong plastic deformation or as delamination of another interface.
Revisiting the “Cdk-Centric” View of the Mammalian Cell Cycle

Since the early genetic studies in yeast, regulation of the cell cycle has been associated to the sequential activation of several proline-directed serine-threonine protein kinases by cyclins. From yeast to humans, the activiy of these cyclin-dependent kinases (Cdks) have been thought to be essential for cell cycle regulation. Recent gene-targeted mouse models for different cyclins and Cdks have shown that members of these families show a certain level of redundancy and that specific complexes are not required for the mitotic cell cycle. However, the complexity of the Cdk-cyclin network and the promiscuity of their members makes it difficult to understand the relative contribution of these proteins to the mammalian cell division cycle. Compensatory roles by non-Cdk activities and Cdk-independent functions of cyclins are increasing the complexity of the current simplistic models. We still do not know whether at least one cyclin-dependent kinase activity is required for cell cycle progression in mammalian cells. Indeed, a relevant question for cancer therapy.
BB0744 Affects Tissue Tropism and Spatial Distribution of Borrelia burgdorferi

ABSTRACT Borrelia burgdorferi, the etiologic agent of Lyme disease, produces a variety of proteins that promote survival and colonization in both the Ixodes species vector and various mammalian hosts. We initially identified BB0744 (also known as p83/100) by screening for B. burgdorferi strain B31 proteins that bind to α1β1 integrin and hypothesized that, given the presence of a signal peptide, BB0744 may be a surface-exposed protein. In contrast to this expectation, localization studies suggested that BB0744 resides in the periplasm. Despite its subsurface location, we were interested in testing whether BB0744 is required for borrelial pathogenesis. To this end, a bb0744 deletion was isolated in a B. burgdorferi strain B31 infectious background, complemented, and queried for the role of BB0744 following experimental infection. A combination of bioluminescent imaging, cultivation of infected tissues, and quantitative PCR (qPCR) demonstrated that Δbb0744 mutant B. burgdorferi bacteria were attenuated in the ability to colonize heart tissue, as well as skin locations distal to the site of infection. Furthermore, qPCR indicated a significantly reduced spirochetal load in distal skin and joint tissue infected with Δbb0744 mutant B. burgdorferi. Complementation with bb0744 restored infectivity, indicating that the defect seen in Δbb0744 mutant B. burgdorferi was due to the loss of BB0744. Taken together, these results suggest that BB0744 is necessary for tissue tropism, particularly in heart tissue, alters the ability of B. burgdorferi to disseminate efficiently, or both. Additional studies are warranted to address the mechanism employed by BB0744 that alters the pathogenic potential of B. burgdorferi.
The burden of chronic obstructive pulmonary disease among employed adults

Objective To examine quality of life, work productivity, and health care resource use among employed adults ages 40–64 years with chronic obstructive pulmonary disease (COPD) in the United States. Methods Data from the 2009 National Health and Wellness Survey were used. All employed adults ages 40–64 years with or without a self-reported diagnosis of COPD were included in the study. Impact on quality of life (using the mental and physical component summary scores and health utilities from the Short Form-12v2), work productivity and activity impairment (using the Work Productivity and Activity Impairment questionnaire), and resource use were analyzed using regression modeling. Results There were 1112 employed adults with COPD versus 18,912 employed adults without COPD. After adjusting for demographics and patient characteristics, adults with COPD reported significantly lower mean levels of mental component summary (46.8 vs 48.5), physical component summary (45.6 vs 49.2), and health utilities (0.71 vs 0.75) than adults without COPD. Workers with COPD reported significantly greater presenteeism (18.9% vs 14.3%), overall work impairment (20.5% vs 16.3%), and impairment in daily activities (23.5% vs 17.9%) than adults without COPD. Employed adults with COPD also reported more mean emergency room visits (0.21 vs 0.12) and more mean hospitalizations (0.10 vs 0.06) in the previous 6 months than employed adults without COPD. All of the above differences were significant at two-sided P < 0.05. Conclusion After adjusting for various confounders, employed adults with COPD reported significantly lower quality of life and work productivity, and increased health care resource utilization than employed adults without COPD. These results highlight the substantial impact and burden of COPD in the United States workforce.
Learning histopathological patterns

Aims: The aim was to demonstrate a method for automated image analysis of immunohistochemically stained tissue samples for extracting features that correlate with patient disease. We address the problem of quantifying tumor tissue and segmenting and counting cell nuclei. Materials and Methods: Our method utilizes a flexible segmentation method based on sparse coding trained from representative image samples. Nuclei counting is based on a nucleus model that takes size, shape, and nucleus probability into account. Nuclei clustering and overlays are resolved using a gray-weighted distance transform. We obtain a probability measure for pixels belonging to a nucleus from our segmentation procedure. Experiments are carried out on two sets of immunohistochemically stained images - one set based on the estrogen receptor (ER) and the other on antigen KI-67. For the nuclei separation we have selected 207 ER image samples from 58 tissue micro array-cores corresponding to 58 patients and 136 KI-67 image samples also from 58 cores. The images are hand-annotated by marking the center position of each nucleus. For the ER data we have a total of 1006 nuclei and for the KI-67 we have 796 nuclei. Segmentation performance was evaluated in terms of missing nuclei, falsely detected nuclei, and multiple detections. The proposed method is compared to state-of-the-art Bayesian classification. Statistical analysis used: The performance of the proposed method and a state-of-the-art algorithm including variations thereof is compared using the Wilcoxon rank sum test. Results: For both the ER experiment and the KI-67 experiment the proposed method exhibits lower error rates than the state-of-the-art method. Total error rates were 4.8 % and 7.7 % in the two experiments, corresponding to an average of 0.23 and 0.45 errors per image, respectively. The Wilcoxon rank sum tests show statistically significant improvements over the state-of-the-art method. Conclusions: We have demonstrated a method and obtained good performance compared to state-of-the-art nuclei separation. The segmentation procedure is simple, highly flexible, and we demonstrate how it, in addition to the nuclei separation, can perform precise segmentation of cancerous tissue. The complexity of the segmentation procedure is linear in the image size and the nuclei separation is linear in the number of nuclei. Additionally the method can be parallelized to obtain high-speed computations.
Spatial Autocorrelation of Communes’ Income Potential in Selected Metropolitan Areas

A commune’s own income potential, indicative of financial self‑sufficiency, underpins the ability of its government to foster local growth. Accurate recognition of the potential levels necessary for improvement of development policies requires that, apart from considering communes’ own potential, neighbouring communes’ potential should be taken into account, especially if the neighbours are large urban centres of substantial demographic and economic capacity. This article aims to examine spatial autocorrelation of income potential of metropolitan communes of Warsaw, Poznan, Wroclaw, and Cracow metro areas in 2014. The study draws on data published by the Central Statistical Office in the Local Data Bank and uses the R programme packages, such as spdep , maptools , and shapefiles for calculations.
Inhibition of T-tropic HIV Strains by Selective Antagonization of the Chemokine Receptor CXCR4

Bicyclams are a novel class of antiviral compounds that are highly potent and selective inhibitors of the replication of HIV-1 and HIV-2. Surprisingly, however, when the prototype compound AMD3100 was tested against M-tropic virus strains such as BaL, ADA, JR-CSF, and SF-162 in human peripheral blood mononuclear cells, the compound was completely inactive. Because of the specific and potent inhibitory effect of AMD3100 on T-tropic viruses, but not M-tropic viruses, it was verified that AMD3100 interacts with the CXC-chemokine receptor CXCR4, the main coreceptor used by T-tropic viruses. AMD3100 dose dependently inhibited the binding of a specific CXCR4 monoclonal antibody to SUP-T1 cells as measured by flow cytometry. It did not inhibit the binding of the biotinylated CC-chemokine macrophage inflammatory protein (MIP) 1α or MIP-1β, ligands for the chemokine receptor CCR5 (the main coreceptor for M-tropic viruses). In addition, AMD3100 completely blocked (a) the Ca2+ flux at 100 ng/ml in lymphocytic SUP-T1 and monocytic THP-1 cells, and (b) the chemotactic responses of THP-1 cells induced by stromal cell–derived factor 1α, the natural ligand for CXCR4. Finally, AMD3100 had no effect on the Ca2+ flux induced by the CC-chemokines MIP-1α, regulated on activation normal T cell expressed and secreted (RANTES; also a ligand for CCR5), or monocyte chemoattractant protein 3 (a ligand for CCR1 and CCR2b), nor was it able to induce Ca2+ fluxes by itself. The bicyclams are, to our knowledge, the first low molecular weight anti-HIV agents shown to act as potent and selective CXCR4 antagonists.
Functional and Structural Analysis of ClC-K Chloride Channels Involved in Renal Disease*

ClC-K channels belong to the CLC family of chloride channels and are predominantly expressed in the kidney. Genetic evidence suggests their involvement in transepithelial transport of chloride in distal nephron segments; ClC-K1 gene deletion leads to nephrogenic diabetes insipidus in mice, and mutations of the hClC-Kb gene cause Bartter's syndrome type III in humans. Expression of rClC-K1 in Xenopus oocytes yielded voltage-independent currents that were pH-sensitive, had a Br− > NO3 − = Cl− > I− conductance sequence, and were activated by extracellular calcium. A glutamate for valine exchange at amino acid position 166 induced strong voltage dependence and altered the conductance sequence of ClC-K1. This demonstrates that rClC-K1 indeed functions as an anion channel. By contrast, we did not detect currents upon hClC-Kb expression in Xenopus oocytes. Using a chimeric approach, we defined a protein domain that, when replaced by that of rClC-K1, allowed the functional expression of a chimera consisting predominantly of hClC-Kb. Its currents were linear and were inhibited by extracellular acidification. Contrasting with rClC-K1, they displayed a Cl− > Br−> I−> NO3 − conductance sequence and were not augmented by extracellular calcium. Insertion of point mutations associated with Bartter's syndrome type III destroyed channel activity. We conclude that ClC-K proteins form constitutively open chloride channels with distinct physiological characteristics.
A preclinical mouse model of glioma with an alternative mechanism of telomere maintenance (ALT)

Glioblastoma multiforme is the most aggressive primary tumor of the central nervous system. Glioma stem cells (GSCs), a small population of tumor cells with stem‐like properties, are supposedly responsible for glioblastoma multiforme relapse after current therapies. In approximately thirty percent of glioblastoma multiforme tumors, telomeres are not maintained by telomerase but through an alternative mechanism, termed alternative lengthening of telomere (ALT), suggesting potential interest in developing specific therapeutic strategies. However, no preclinical model of ALT glioma was available until the isolation of TG20 cells from a human ALT glioma. Herein, we show that TG20 cells exhibit a high level of telomeric recombination but a stable karyotype, indicating that their telomeres retain their protective function against chromosomal instability. TG20 cells possess all of the characteristic features of GSCs: the expression of neural stem cell markers, the generation of intracerebral tumors in NOD‐SCID‐IL2Rγ (NSG) mice as well as in nude mice, and the ability to sustain serial intracerebral transplantations without expressing telomerase, demonstrating the stability of the ALT phenotype in vivo. Furthermore, we also demonstrate that 360B, a G‐quadruplex ligand of the pyridine derivative series that impairs telomere replication and mitotic progression in cancer cells, prevents the development of TG20 tumors. Together, our results show that intracerebral grafts of TG20 cells in immunodeficient mice constitute an efficient preclinical model of ALT glioblastoma multiforme and that G‐quadruplex ligands are a potential therapy for this specific type of tumor.