gebhart/patrepeval huggingface dataset:
Monocyte Subset Dynamics in Human Atherosclerosis Can Be Profiled with Magnetic Nano-Sensors (2009)

Monocytes are circulating macrophage and dendritic cell precursors that populate healthy and diseased tissue. In humans, monocytes consist of at least two subsets whose proportions in the blood fluctuate in response to coronary artery disease, sepsis, and viral infection. Animal studies have shown that specific shifts in the monocyte subset repertoire either exacerbate or attenuate disease, suggesting a role for monocyte subsets as biomarkers and therapeutic targets. Assays are therefore needed that can selectively and rapidly enumerate monocytes and their subsets. This study shows that two major human monocyte subsets express similar levels of the receptor for macrophage colony stimulating factor (MCSFR) but differ in their phagocytic capacity. We exploit these properties and custom-engineer magnetic nanoparticles for ex vivo sensing of monocytes and their subsets. We present a two-dimensional enumerative mathematical model that simultaneously reports number and proportion of monocyte subsets in a small volume of human blood. Using a recently described diagnostic magnetic resonance (DMR) chip with 1 microl sample size and high throughput capabilities, we then show that application of the model accurately quantifies subset fluctuations that occur in patients with atherosclerosis.
Preclinical Evaluation of the WEE1 Inhibitor MK-1775 as Single-Agent Anticancer Therapy (2013)

Inhibition of the DNA damage checkpoint kinase WEE1 potentiates genotoxic chemotherapies by abrogating cell-cycle arrest and proper DNA repair. However, WEE1 is also essential for unperturbed cell division in the absence of extrinsic insult. Here, we investigate the anticancer potential of a WEE1 inhibitor, independent of chemotherapy, and explore a possible cellular context underlying sensitivity to WEE1 inhibition. We show that MK-1775, a potent and selective ATP-competitive inhibitor of WEE1, is cytotoxic across a broad panel of tumor cell lines and induces DNA double-strand breaks. MK-1775-induced DNA damage occurs without added chemotherapy or radiation in S-phase cells and relies on active DNA replication. At tolerated doses, MK-1775 treatment leads to xenograft tumor growth inhibition or regression. To begin addressing potential response markers for MK-1775 monotherapy, we focused on PKMYT1, a kinase functionally related to WEE1. Knockdown of PKMYT1 lowers the EC(50) of MK-1775 by five-fold but has no effect on the cell-based response to other cytotoxic drugs. In addition, knockdown of PKMYT1 increases markers of DNA damage, γH2AX and pCHK1(S345), induced by MK-1775. In a post hoc analysis of 305 cell lines treated with MK-1775, we found that expression of PKMYT1 was below average in 73% of the 33 most sensitive cell lines. Our findings provide rationale for WEE1 inhibition as a potent anticancer therapy independent of a genotoxic partner and suggest that low PKMYT1 expression could serve as an enrichment biomarker for MK-1775 sensitivity.
ATLAS liquid argon calorimeter front end electronics (2008)

The ATLAS detector has been designed for operation at CERN's Large Hadron Collider.ATLAS includes a complex system of liquid argon calorimeters.This paper describes the architecture and implementation of the system of custom front end electronics developed for the readout of the ATLAS liquid argon calorimeters.
Effects of feeding level on nutrient digestibility and enteric methane production in growing goats (&lt;i&gt;Capra hircus hircus) and Sika deer (Cervus nippon hortulorum) (2018)

Increasing the feeding level increased CH4 production in both goats and Sika deer, and predictive models of enteric CH4 production by goats and Sika deer were estimated.
Bolocam Survey for 1.1 mm Dust Continuum Emission in the c2d Legacy Clouds. II. Ophiuchus (2006)

We present a large-scale millimeter continuum map of the Ophiuchus molecular cloud. Nearly 11 deg2, including all of the area in the cloud with AV ≥ 3 mag, was mapped at 1.1 mm with Bolocam on the Caltech Submillimeter Observatory (CSO). By design, the map also covers the region mapped in the infrared with the Spitzer Space Telescope. We detect 44 definite sources, and a few likely sources are also seen along a filament in the eastern streamer. The map indicates that dense cores in Ophiuchus are very clustered and often found in filaments within the cloud. Most sources are round, as measured at the half-power point, but elongated when measured at lower contour levels, suggesting spherical sources lying within filaments. The masses, for an assumed dust temperature of 10 K, range from 0.24 to 3.9 M☉, with a mean value of 0.96 M☉. The total mass in distinct cores is 42 M☉, 0.5%-2% of the total cloud mass, and the total mass above 4 σ is about 80 M☉. The mean densities in the cores are quite high, with an average of 1.6 × 106 cm-3, suggesting short free-fall times. The core mass distribution can be fitted with a power law with slope α = 2.1 ± 0.3 for M &gt; 0.5 M☉, similar to that found in other regions, but slightly shallower than that of some determinations of the local IMF. In agreement with previous studies, our survey shows that dense cores account for a very small fraction of the cloud volume and total mass. They are nearly all confined to regions with AV ≥ 9 mag, a lower threshold than found previously.
Reexpression of Tumor Suppressor, sFRP1, Leads to Antitumor Synergy of Combined HDAC and Methyltransferase Inhibitors in Chemoresistant Cancers (2012)

Metastatic solid tumors are aggressive and mostly drug resistant, leading to few treatment options and poor prognosis as seen with clear cell renal cell carcinoma (ccRCC) and triple-negative breast cancer (TNBC). Therefore, the identification of new therapeutic regimes for the treatment of metastatic disease is desirable. ccRCC and TNBC cell lines were treated with the HDAC inhibitor romidepsin and the methyltransferase inhibitor decitabine, two epigenetic modifying drugs approved by the U.S. Food and Drug Administration for the treatment of various hematologic malignancies. Cell proliferation analysis, flow cytometry, quantitative PCR, and immunoblotting techniques were used to evaluate the antitumor synergy of this drug combination and identify the reexpression of epigenetically silenced tumor suppressor genes. Combinatorial treatment of metastatic TNBC and stage IV ccRCC cell lines with romidepsin/decitabine leads to synergistic inhibition of cell growth and induction of apoptosis above levels of individual drug treatments alone. Synergistic reexpression of the tumor suppressor gene secreted frizzled-related protein one (sFRP1) was observed in combinatorial drug-treated groups. Silencing sFRP1 (short hairpin RNA) before combinatorial drug treatment showed that sFRP1 mediates the growth inhibitory and apoptotic activity of combined romidepsin/decitabine. Furthermore, addition of recombinant sFRP1 to ccRCC or TNBC cells inhibits cell growth in a dose-dependent manner through the induction of apoptosis, identifying that epigenetic silencing of sFRP1 contributes to renal and breast cancer cell survival. Combinatorial treatment with romidepsin and decitabine in drug resistant tumors is a promising treatment strategy. Moreover, recombinant sFRP1 may be a novel therapeutic strategy for cancers with suppressed sFRP1 expression.
Image registration by minimization of Mapping Complexity (2009)

The criterion for the correct spatial alignment is a key component in image registration. We formulate the registration problem as one that finds the spatial and intensity mappings of minimal complexity that make images exactly equal. We do not assume any parametric forms of these functions, and estimate them within variational calculus. We analytically solve for non-stationary intensity mapping, eliminate it from the objective function and arrive with a new similarity measure. We name it the mapping complexity (MC) similarity measure, because it achieves the optimum when intensity and spatial mappings are of minimal complexity. Due to its general formulation, the similarity measure works both for complex intensity relationships (e.g. multimodal registration) and for spatially-varying intensity distortions. Our similarity measure can be interpreted as the one that favors one image to lie mostly within a span of the leading eigenvectors of the kernel matrix, where the kernel matrix is constructed from the second image. We introduce a fast algorithm to compute the similarity measure. In particular, we introduce a fast kernel vector product (FKVP) algorithm, which is of general interest in computer vision. We demonstrate the accuracy of the new similarity measure on several mono- and multi-modal examples with complex intensity non-uniformities.
Mean Nearest-Neighbor Distance in Random Packings of HardD-Dimensional Spheres (1995)

We derive the first nontrivial rigorous bounds on the mean distance between nearest neighbors $\ensuremath{\lambda}$ in ergodic, isotropic packings of hard $D$-dimensional spheres that depend on the packing fraction and nearest-neighbor distribution function. Several interesting implications of these bounds for equilibrium as well as nonequilibrium ensembles are explored. For an equilibrium ensemble, we find accurate analytical approximations for $\ensuremath{\lambda}$ for $D\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2$ and 3 that apply up to random close packing. Our theoretical results are in excellent agreement with available computer-simulation data.
Symptomatic ectopic bone formation after off-label use of recombinant human bone morphogenetic protein-2 in transforaminal lumbar interbody fusion (2009)

Although previously believed to be only a radiographic finding, the development of ectopic bone following rhBMP-2 use in lumbar fusion can be clinically significant. This paper describes 4 cases of delayed neural compression following MIS-TLIF. The reader should be aware of this potential complication following the off-label use of rhBMP-2 in the lumbar spine.
Assessment of acquired mucociliary clearance defects using micro‐optical coherence tomography (2017)

Background Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance (MCC) in sinonasal epithelium, which may lead to chronic rhinosinusitis (CRS). Abnormal chloride (Cl − ) transport is one such mechanism that contributes to this disorder and can be acquired secondary to environmental perturbations, such as hypoxia at the tissue surface. The objective of this study was to assess the technological feasibility of the novel micro‐optical coherence tomography (μOCT) imaging technique for investigating acquired MCC defects in cultured human sinonasal epithelial (HSNE) cells. Methods Primary HSNE cell cultures were subjected to a 1% oxygen environment for 12 hours to induce acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Ion transport characteristics were assessed with pharmacologic manipulation in Ussing chambers. ASL, periciliary fluid (PCL), and ciliary beat frequency (CBF) were evaluated using μOCT. Results Amiloride‐sensitive transport (ΔI SC ) was greater in cultures exposed to hypoxia (hypoxia: −13.2 ± 0.6 μA/cm 2 ; control: −6.5 ± 0.1 μA/cm 2 ; p &lt; 0.01), whereas CFTR‐mediated anion transport was significantly diminished (hypoxia: 28.6 ± 0.3 μA/cm 2 ; control: 36.2 ± 1.6 μA/cm 2 ; p &lt; 0.01), consistent with acquired CFTR dysfunction and sodium hyperabsorption. Hypoxia diminished all markers of airway surface function microanatomy as observed with μOCT, including ASL (hypoxia: 5.0 ± 0.4 μm; control: 9.0 ± 0.9 μm; p &lt; 0.01) and PCL depth (hypoxia: 2.5 ± 0.1 μm; control: 4.8 ± 0.3 μm; p &lt; 0.01), and CBF (hypoxia: 8.7 ± 0.3 Hz; control: 10.2 ± 0.3 Hz; p &lt; 0.01). Conclusion Hypoxia‐induced defects in epithelial anion transport in HSNE led to predictable effects on markers of MCC measured with novel μOCT imaging. This imaging method represents a technological leap forward and is feasible for assessing acquired defects impacting the airway surface.
The US national registry for childhood interstitial and diffuse lung disease: Report of study design and initial enrollment cohort (2023)

This Registry is the largest longitudinal chILD cohort in the United States to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.
Developmental fate in chimeras derived from highly asynchronous murine blastomeres (1987)

The developmental fate of single blastomeres from eight-cell murine embryos reaggregated with intact two-cell embryos was evaluated after culture. Fluorescein isothiocyanate was used to follow developmental fate in preblastocyst chimeric embryos. Expression of stage-specific embryonic antigen 3 was used to assay developmental fate at the blastocyst stage, and glucosephosphate isomerase variants were used to assay at the blastocyst stage and after implantation. The results suggest that the descendents of the 1/8 component stay in a patch area and do not selectively migrate to the inner cell mass (ICM). This is in contrast to many studies that indicate that smaller blastomeres, which are more advanced in development, migrate to the ICM. The differences in experimental designs are discussed. Possible mechanisms for this phenomena are that the eight-cell blastomere is physically excluded from the ICM by position or polarization, or that it is differentiating ahead of the two-cell component and becomes trophectoderm.
IMO-3100, an Antagonist of Toll-Like Receptors 7 and 9, Modulates Gene Expression and Regulatory Networks Induced by Ligands (48.25) (2009)

Abstract In autoimmune diseases, immune complexes containing self-nucleic acids have been shown to induce inflammatory responses through TLR7 and 9. IMO-3100 is a novel DNA-based antagonist of TLR7 and 9 that is shown to inhibit TLR7- and 9-mediated immune responses. To elucidate inhibitory effects of IMO-3100 on TLR7 and 9 agonist-mediated gene expression, we treated human PBMCs with a TLR7 or TLR9 agonist with or without IMO-3100, isolated total RNA, carried out gene expression profiling on human inflammatory response and autoimmunity microarray, and analyzed data to identify changes in regulatory networks. IMO-3100 alone showed insignificant up-regulation of a small number of genes. TLR9 agonist significantly up-regulated a number of genes, including IP-10, MyD88, MCP-1, IL-6, IRF7, IL-17A, NF-κB1, and RIPK2, which regulate immune responses, NF-κB signaling, inflammation, and chemotaxis networks. TLR7 agonist showed a different gene expression profile compared with TLR9 agonist. The genes that were significantly up-regulated by TLR7 agonist include IP-10, IRF7, IFN-α1, IFN-α4, IFN-γ, IL-15Ra, IL-17A, IL-6, and TIRAP, which regulate host defense response, chemotaxis, and cytokine and chemokine signaling pathways. Co-incubation of IMO-3100 with either TLR agonist resulted in inhibition of genes that were up-regulated with either TLR agonist alone. These results indicate that TLR7 and 9 agonists induce different gene expression profiles and IMO-3100 is a potent inhibitor of these responses. IMO-3100 is a lead candidate identified for development for potential applications in autoimmune diseases.
[NK cell-based immunotherapy: new prospects and involvement of dendritic cells]. (2003)

Dendritic cells (DC) were initially described as antigen presenting cells able to prime naive T cells. In fact, dendritic cells are also able to activate natural killer (NK) cells. The crosstalk between DC and NK is now regarded as a main stage in the initiation of innate and adaptative immune responses. Moreover, DC mediated-NK cell activation is particularly efficient since DC promote both effector functions and survival or proliferation of NK cells. Furthermore, recent publications in the field of NK cell biology underscore a role for NK cells in anti-tumor effects. NK cell-based immunotherapy should be reconsidered Here, we will report how pioneering immunotherapy trials based on natural cytotoxicity and progress in NK cell biology can promote NK cells in anti-tumor immune responses. Then, we will discuss the biological features of the DC/NK crosstalk and its implementations in immunotherapy protocols.
Novel structural-scale uncertainty measures and error retention curves: application to multiple sclerosis (2022)

This paper focuses on the uncertainty estimation for white matter lesions (WML) segmentation in magnetic resonance imaging (MRI). On one side, voxel-scale segmentation errors cause the erroneous delineation of the lesions; on the other side, lesion-scale detection errors lead to wrong lesion counts. Both of these factors are clinically relevant for the assessment of multiple sclerosis patients. This work aims to compare the ability of different voxel- and lesion-scale uncertainty measures to capture errors related to segmentation and lesion detection, respectively. Our main contributions are (i) proposing new measures of lesion-scale uncertainty that do not utilise voxel-scale uncertainties; (ii) extending an error retention curves analysis framework for evaluation of lesion-scale uncertainty measures. Our results obtained on the multi-center testing set of 58 patients demonstrate that the proposed lesion-scale measure achieves the best performance among the analysed measures. All code implementations are provided at https://github.com/NataliiaMolch/MS_WML_uncs
Laser interaction and related plasma phenomena (Report on the 9th International Workshop, Monterey, CA, 6-10 November 1989) (1990)

The 9th International Workshop on Laser Interaction and Related Plasma Phenomena was held from 6 to 10 November 1989, at Naval Postgraduate School, Monterey, California. This series of meetings began in 1969 and it is the longest series of meetings in this field in the USA. It is, in fact, the longest series with published proceedings that document the advances and the growth of this dynamic field of physics and technology.
Viral infection switches the balance between bacterial and eukaryotic recyclers of organic matter during coccolithophore blooms (2023)

Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global elemental cycling. Upon demise of the bloom, organic carbon is partly respired and partly transferred to either higher trophic levels, bacterial biomass production or sinking. Viral infection can lead to bloom termination, but its impact on the fate of carbon remains largely unquantified. Here, we characterize the interplay between viral infection and the composition of a bloom-associated microbiome and consequently the evolving biogeochemical landscape, by conducting a large-scale mesocosm experiment where we monitor seven induced coccolithophore blooms. The blooms show different degrees of viral infection and reveal that only high levels of viral infection are followed by significant shifts in the composition of free-living bacterial and eukaryotic assemblages. Intriguingly, upon viral infection the biomass of eukaryotic heterotrophs (thraustochytrids) rivals that of bacteria as potential recyclers of organic matter. By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection causes a 2-4 fold increase in per-cell rates of extracellular carbon release in the form of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms.
CXCL17 is a Prognostic Biomarker That Distinguishes Severe Pandemic InfluenzaA(H1N1) from COVID-19 (2020)

Abstract BackgroundCXCL17 is chemotactic for myeloid cells, exhibits broad-spectrum bactericidal activity, and is expressed in mucosal tissues. This chemokine is constitutively expressed in the respiratory tract, suggesting a role for CXCL17 in lung defenses. However, little is known about the possible participation of CXCL17 during respiratory infections in humans. Here, we evaluated the role of CXCL17 as a biomarker in patients with severe pandemic influenza A(H1N1) and coronavirus disease 2019 (COVID-19). MethodsWe conducted a prospective cohort study in hospitalized patients with severe influenza A(H1N1) and COVID-19 admitted to two national reference centers in Mexico City. Peripheral blood samples were obtained on admission for determinations of the serum levels of CXCL17 by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 in lung autopsy specimens from patients that succumbed to both diseases was assessed by immunohistochemistry (IHQ). Serum CXCL17 levels were compared between patients grouped according to their disease and clinical outcome. The diagnostic and predictive value of serum CXCL17 levels was evaluated using machine-learning algorithms and regression analyses. ResultsA total of 92 patients were enrolled in the study, from which 68 were infected with influenza and 24 had COVID-19. Their clinical characteristics were similar, although dyspnea, rhinorrhea, and sputum production were more common during influenza, whereas dry cough and vomit were more frequent among COVID-19 patients. Both diseases induced the local expression of CXCL17 in the lung. However, serum levels of CXCL17 were increased only in patients with influenza but not COVID-19. CXCL17 not only differentiates influenza from COVID-19 but serves as a prognostic biomarker associated with mortality and renal failure in influenza patients. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages produce CXCL17 after influenza A(H1N1) pdm09 virus infection. ConclusionsOur results suggest a possible role for CXCL17 in the pathogenesis of influenza A(H1N1), supporting the use of this molecule as a prognostic biomarker. Future studies on the role of CXCL17 in COVID-19 are warranted.
Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae causing meningitis in Egypt, 1998–2003 (2005)

Resistance to penicillin may be increasing among S. pneumoniae strains causing meningitis in Egypt, and a moderate proportion of these strains are not covered by current pneumococcal conjugate vaccines. In addition to intensifying education efforts about judicious use of antibiotics, laboratory-based surveillance for other forms of invasive pneumococcal disease, especially pneumonia, is needed before decisions can be made regarding the most effective vaccines for control of this disease in Egypt.