gebhart/patrepeval huggingface dataset:
Biological responses of human mesenchymal stem cells to titanium wear debris particles (2011)

Wear debris-induced osteolysis is a major cause of orthopedic implant aseptic loosening, and various cell types, including macrophages, monocytes, osteoblasts, and osteoclasts, are involved. We recently showed that mesenchymal stem/osteoprogenitor cells (MSCs) are another target, and that endocytosis of titanium (Ti) particles causes reduced MSC proliferation and osteogenic differentiation. Here we investigated the mechanistic aspects of the endocytosis-mediated responses of MSCs to Ti particulates. Dose-dependent effects were observed on cell viability, with doses >300 Ti particles/cell resulting in drastic cell death. To maintain cell viability and analyze particle-induced effects, doses <300 particles/cell were used. Increased production of interleukin-8 (IL-8), but not IL-6, was observed in treated MSCs, while levels of TGF-β, IL-1β, and TNF-α were undetectable in treated or control cells, suggesting MSCs as a likely major producer of IL-8 in the periprosthetic zone. Disruptions in cytoskeletal and adherens junction organization were also observed in Ti particles-treated MSCs. However, neither IL-8 and IL-6 treatment nor conditioned medium from Ti particle-treated MSCs failed to affect MSC osteogenic differentiation. Among other Ti particle-induced cytokines, only GM-CSF appeared to mimic the effects of reduced cell viability and osteogenesis. Taken together, these results strongly suggest that MSCs play both responder and initiator roles in mediating the osteolytic effects of the presence of wear debris particles in periprosthetic zones.
Folic acid-mediated inhibition of serum-induced activation of EGFR promoter in colon cancer cells (2004)

Although accumulating evidence suggests a chemopreventive role for folic acid (FA) in colorectal carcinogenesis, the underlying mechanisms are largely unknown. Previously, we reported that supplemental FA inhibits the expression and activation of epidermal growth factor receptor (EGFR) in colon cancer cell lines. To determine the mechanism(s) by which FA affects EGFR function, we have examined whether and to what extent supplemental FA or its metabolites 5-methyltetrahydrofolate (MTF), dihydrofolate (DF), and tetrahydrofolate (TF) will modulate basal and serum-induced activation of the EGFR promoter in the HCT-116 colon cancer cell line. HCT-116 cells were preincubated with or without (control) FA or one of its metabolites (10 microg/ml) for 48 h, transfected with the EGFR promoter luciferase reporter construct, and incubated for 48 h with FA, DF, TF, or 5-MTF in the absence or presence of 10% FBS. Supplemental FA as well as its metabolites markedly inhibited EGFR promoter activity and its methylation status. Exposure of the cells to 10% FBS caused a marked stimulation of EGFR promoter activity and its expression, both of which were greatly abrogated by supplemental FA and 5-MTF. In contrast, serum-induced activation of c-fos promoter activity was unaffected by 5-MTF. The 5-MTF-induced inhibition of serum-mediated stimulation of EGFR promoter activity and EGFR expression was reversed when methylation was inhibited by 5-aza-2'-deoxycytidine. Our data suggest that FA and its metabolite 5-MTF inhibit EGFR promoter activity in colon cancer cells by enhancing methylation. This could partly be responsible for FA-mediated inhibition of growth-related processes in colorectal neoplasia.
Analytical Chemistry for Homeland Defense and National Security (2002)

The budget was requested to support speaker expenses to attend and speak in the day long symposium at the ACS meeting. The purpose of the symposium was to encourage analytical chemists to contribute to national security.
Online parameter estimation in dynamic Markov Random Fields for image sequence analysis (2012)

Markov Random Fields (MRF) have proven to be extremely useful models for efficient and accurate image segmentation.Recent literature points to an increased effort towards incorporating useful priors (shape, geometry, context) in a MRF framework. However, topological priors, considered extremely crucial in biological and natural image sequences have been less explored. This work proposes a strategy wherein free parameters of the MRF are used to make it topology aware using a semantic graphical model working in conjunction with the MRF. Estimation of free parameters is constrained by prior knowledge of an object's topological dynamics encoded by the graphical model. Maximizing a regional conformance measure yields parameters for the frame under consideration. The application motivating this work is the tracing of neuronal structures across 3D serial section Transmission Electron Micrograph (ssTEM) stacks. Applicability of the proposed method is demonstrated by tracing 3D structures in ssTEM stacks.
An Efficient Delivery Scheme for Coded Caching (2015)

We consider a network with several users trying to access a database of files stored at a server through a shared link. Each user is equipped with a cache, where files can be prefetched according to a caching policy which is mainly based on the popularities of the files. Coded caching tries to exploit coding opportunities created by cooperative caching and has been shown to significantly reduce the load on the shared link. Most of the prior works focused on optimizing the caching policy so as to minimize this expected load. Given the caching policy and the user demands, the problem of minimizing the load over the shared link is essentially an index coding problem. In this paper, we design a novel delivery scheme that builds on a prior scheme for the uniform demand case, but performs better in the non-uniform demand case. We also evaluate this delivery scheme for different caching policies.
Divide-and-Evolve: a New Memetic Scheme for Domain-Independent Temporal\n Planning (2006)

An original approach, termed Divide-and-Evolve is proposed to hybridize\nEvolutionary Algorithms (EAs) with Operational Research (OR) methods in the\ndomain of Temporal Planning Problems (TPPs). Whereas standard Memetic\nAlgorithms use local search methods to improve the evolutionary solutions, and\nthus fail when the local method stops working on the complete problem, the\nDivide-and-Evolve approach splits the problem at hand into several, hopefully\neasier, sub-problems, and can thus solve globally problems that are intractable\nwhen directly fed into deterministic OR algorithms. But the most prominent\nadvantage of the Divide-and-Evolve approach is that it immediately opens up an\navenue for multi-objective optimization, even though the OR method that is used\nis single-objective. Proof of concept approach on the standard\n(single-objective) Zeno transportation benchmark is given, and a small original\nmulti-objective benchmark is proposed in the same Zeno framework to assess the\nmulti-objective capabilities of the proposed methodology, a breakthrough in\nTemporal Planning.\n
Targeting the AnxA1/Fpr2/ALX pathway regulates neutrophil function, promoting thromboinflammation resolution in sickle cell disease (2021)

Neutrophils play a crucial role in the intertwined processes of thrombosis and inflammation. An altered neutrophil phenotype may contribute to inadequate resolution, which is known to be a major pathophysiological contributor of thromboinflammatory conditions such as sickle cell disease (SCD). The endogenous protein annexin A1 (AnxA1) facilitates inflammation resolution via formyl peptide receptors (FPRs). We sought to comprehensively elucidate the functional significance of targeting the neutrophil-dependent AnxA1/FPR2/ALX pathway in SCD. Administration of AnxA1 mimetic peptide AnxA1Ac2-26 ameliorated cerebral thrombotic responses in Sickle transgenic mice via regulation of the FPR2/ALX (a fundamental receptor involved in resolution) pathway. We found direct evidence that neutrophils with SCD phenotype play a key role in contributing to thromboinflammation. In addition, AnxA1Ac2-26 regulated activated SCD neutrophils through protein kinase B (Akt) and extracellular signal-regulated kinases (ERK1/2) to enable resolution. We present compelling conceptual evidence that targeting the AnxA1/FPR2/ALX pathway may provide new therapeutic possibilities against thromboinflammatory conditions such as SCD.
Physicochemical Characterization of Zeolites SSZ-26 and SSZ-33 (1994)

Detailed characterization of zeolites SSZ-26 and SSZ-33 is presented and includes data from adsorption experiments, X-ray powder diffraction (XRD), electron diffraction (ED), and high-resolution electron microscopy (HREM). Simulated XRD patterns and HREM images of the proposed structures agree very well with all the experimental data. These zeolites are the first synthetic high-silica molecular sieves to contain a three-dimensional pore system comprised of intersecting 10- and 12-ring pores. The structures of&#13;\nSSZ-26 and SSZ-33 are compared to the structures of known zeolites, and the relationships between the geometry of the structure-directing agents used in the synthesis of SSZ-26 and the geometry of the pores are analyzed using energy minimization calculations. Several hypothetical zeolite structures are derived based on the proposed models for SSZ-26 and SSZ-33. SSZ-26 and SSZ-33 are the first examples of molecular sieves whose multidimensional pore systems have been formed by the purposeful design of their structure-directing agents.
Prognosis Associated With Luminal and Basal Subtypes of Metastatic Prostate Cancer (2021)

These findings represent the largest integrated clinical, transcriptomic, and genomic analysis of mCRPC samples to date, and suggest that mCRPC can be classified as luminal and basal tumors. Analogous to primary prostate cancer, these data suggest that the benefit of ASI treatment is more pronounced in luminal tumors and support the use of ASIs in this population. In the basal tumors, a chemotherapeutic approach could be considered in some patients given the similarity to SCNC and the diminished benefit of ASI therapy. Further validation in prospective clinical trials is warranted.
Aerosol delivery of synthetic lung surfactant (2014)

Background. Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in premature infants with respiratory distress syndrome due to lack of lung surfactant. If this approach fails, the next step is often intubation, mechanical ventilation (MV) and intratracheal instillation of clinical lung surfactant. Objective. To investigate whether aerosol delivery of advanced synthetic lung surfactant, consisting of peptide mimics of surfactant proteins B and C (SP-B and SP-C) and synthetic lipids, during nCPAP improves lung function in surfactant-deficient rabbits. Methods. Experimental synthetic lung surfactants were produced by formulating 3% Super Mini-B peptide (SMB surfactant), a highly surface active SP-B mimic, and a combination of 1.5% SMB and 1.5% of the SP-C mimic SP-Css ion-lock 1 (BC surfactant), with a synthetic lipid mixture. After testing aerosol generation using a vibrating membrane nebulizer and aerosol conditioning (particle size, surfactant composition and surface activity), we investigated the effects of aerosol delivery of synthetic SMB and BC surfactant preparations on oxygenation and lung compliance in saline-lavaged, surfactant-deficient rabbits, supported with either nCPAP or MV. Results. Particle size distribution of the surfactant aerosols was within the 1-3 µm distribution range and surfactant activity was not affected by aerosolization. At a dose equivalent to clinical surfactant therapy in premature infants (100 mg/kg), aerosol delivery of both synthetic surfactant preparations led to a quick and clinically relevant improvement in oxygenation and lung compliance in the rabbits. Lung function recovered to a greater extent in rabbits supported with MV than with nCPAP. BC surfactant outperformed SMB surfactant in improving lung function and was associated with higher phospholipid values in bronchoalveolar lavage fluid; these findings were irrespective of the type of ventilatory support (nCPAP or MV) used. Conclusions. Aerosol delivery of synthetic lung surfactant with a combination of highly active second generation SP-B and SP-C mimics was effective as a therapeutic approach towards relieving surfactant deficiency in spontaneously breathing rabbits supported with nCPAP. To obtain similar results with nCPAP as with intratracheal instillation, higher dosage of synthetic surfactant and reduction of its retention by the delivery circuit will be needed to increase the lung dose.
The complexities of grasping in the wild (2018)

The recent ubiquity of high-framerate (120 fps and higher) handheld cameras creates the opportunity to study human grasping at a greater level of detail than normal speed cameras allow. We first collected 91 slow-motion interactions with objects in a convenience store setting. We then annotated the actions through the lenses of various existing manipulation taxonomies. We found manipulation, particularly the process of forming a grasp, is complicated and proceeds quickly. Our dataset shows that there are many ways that people deal with clutter in order to form a strong grasp of an object. It also reveals several errors and how people recover from them. Though annotating motions in detail is time-consuming, the annotation systems we used nevertheless leave out important aspects of understanding manipulation actions, such as how the environment is functioning as a 'finger' of sorts, how different parts of the hand can be involved in different grasping tasks, and high-level intent.
An Investigation of Dose Estimates inside a Space Station Using Solar Protons Spectrum (2012)

This paper investigates the interaction of energetic solar protons measured by the Geostationary Operational Environmental Satellites (GOES), with the aluminum shielding structure of different thicknesses and calculates the dose distribution inside an tissue equivalent phantom inside the aluminum structure. In addition to the incident energetic protons, the major contributors to the total dose inside the phantom are the secondary protons and neutrons generated by spallation reactions in the aluminum structure and the phantom. Three modes of incidence of source protons are considered: center seeking, planar, and isotropic. The center seeking mode is the most conservative, resulting in the highest dose values and distribution inside the phantom, compared to those at the phantom’s outer surface. Both the planar and isotropic modes result in much lower dose values that are more evenly distributed throughout the phantom.
Isolation and characterization of two novel A20-like proteins (2001)

The transcription factor nuclear factor κB (NF-κB) plays a pivotal role in inflammatory processes through induction of adhesion molecules and chemokines. The zinc finger molecule A20 is an important negative regulator of NF-κB. The mechanism utilized by A20 is not fully understood, but A20 has been shown to bind to tumour-necrosis-factor-receptor-associated factor (TRAF) molecules, which are necessary for pro-inflammatory cytokine signalling. We report two novel genes, Cezanne (cellular zinc finger anti-NF-kB) and TRABID (TRAF-bnding domain), with sequence similarity to A20. Co-immunoprecipitation studies indicated that TRAF6 was able to interact with both Cezanne and TRABID. In contrast, reporter gene experiments revealed a specific ability of Cezanne to down-regulate NF-κB. It is likely, therefore, that Cezanne participates in the regulation of inflammatory processes.
P2‐405: Induction of toll‐like receptor 9 signaling as a method for preventing or ameliorating Alzheimer's disease (2008)

Several vaccination approaches are effective in reducing amyloid accumulation and associated cognitive deficits in Alzheimer's disease (AD) mice model by stimulating humoral or cellular responses of the adaptive immune system. The stimulation of innate immunity as a therapeutic approach has been less studied. The Toll-like receptors (TLRs) are a family of innate immune mediators that are expressed by a variety of immune and non-immune cells. Recent results from our research group and others indicate that stimulation of TLR9 signaling by peripheral administration of a TLR ligand effectively delays progression of prion disease, a disease that shares mechanistic similarities with AD. We sought to determine whether peripheral administration of a TLR9 agonist CpG oligodeoxynucleotide (ODN) can reduce amyloid burden and alleviate cognitive deficits in AD mice model. Female APP Tg2576 mice were injected with either TLR9 agonist (type B CpG ODN 1826) or vehicle beginning at 6 weeks of age, and once a month thereafter for a total of 14 injections. Controls were non-transgenic C57BL/6 × SJL mice injected with vehicle on the same schedule. At the age of 16 months, the mice were subjected to behavioral testing. No difference between transgenic (Tg) groups was found in any locomotor parameters. CpG ODN treatment led to working memory improvement in Tg2576 mice as indicating by radial arm maze testing (one-way ANOVA p=0.0073, post-hoc Tg-CpG vs Tg-vehicle, p<0.05). Improvement in object recognition was also observed in the CpG ODN treated mice (Tg-CpG ODN vs Tg-vehicle, p=0.054). In evaluating the efficacy of CpG ODN administration in AD mice, we found that stimulation of TLR9 signaling led to 66% (p=0.0001) reduction in cortical and 59% (p=0.002) reduction in hippocampal amyloid burden as compared to vehicle treated Tg animals. The remarkable reduction of amyloid burden was paralleled by an overall reduction in CD45 and CD11b microglial immunoreactivity. These results validate the feasibility of stimulation of innate immunity through TLR9 signaling with CpG DNA as a novel immunotherapeutic approach for AD.
The Sorghum bicolor genome and the diversification of grasses (2009)

Sorghum, an African grass related to sugar cane and maize, is grown for food, feed, fibre and fuel. We present an initial analysis of the -730-megabase Sorghum bicolor (L.) Moench genome, placing -98% of genes in their chromosomal context using whole-genome shotgun sequence validated by genetic, physical and syntenic information. Genetic recombination is largely confined to about one-third of the sorghum genome with gene order and density similar to those of rice. Retrotransposon accumulation in recombinationally recalcitrant heterochromatin explains the -75% larger genome size of sorghum compared with rice. Although gene and repetitive DNA distributions have been preserved since palaeopolyploidization ~70 million years ago, most duplicated gene sets lost one member before the sorghum-rice divergence. Concerted evolution makes one duplicated chromosomal segment appear to be only a few million years old. About 24% of genes are grass-specific and 7% are sorghum-specific. Recent gene and microRNA duplications may contribute to sorghum's drought tolerance
The Cholinergic Anti-Inflammatory Pathway as a Conceptual Framework to Treat Inflammation-Mediated Renal Injury (2019)

With the awareness that the cholinergic anti-inflammatory pathway serves to prevent or limit inflammation in peripheral organs, vagus nerve stimulation has become a promising strategy in the treatment of several inflammatory conditions. Both pharmacological and non-pharmacological methods have been used in many studies to limit organ injury as a consequence of inflammation. Key Messages: In this review, we will highlight our current knowledge of the cholinergic anti-inflammatory pathway, with emphasis on its potential clinical use in the treatment of inflammation-triggered kidney injury.
Overlay improvement in nanoimprint lithography for 1×-nm patterning (2016)

Nanoimprint lithography (NIL) is becoming a promising technique for fine-patterning with a lower cost than other lithography techniques. High overlay accuracy is one of the issues in NIL. Using die-by-die alignment with moiré fringe detection, an NIL alignment measurement accuracy below 1 nm and an overlay accuracy below 5 nm have been reported. On the other hand, the requirement for overlay in 2020 is estimated to be 3–4 nm for dynamic random access memory, flash and logic devices. In order to make the overlay accuracy requirement qualify from the semiconductor industry, a lot of technology enhancements, such as the improvement of overlay control accuracy for NIL-tools, image placement accuracy improvement for NIL templates, mix and match technique of NIL, and other lithography tools such as immersion exposure ones, are needed. In this paper, the authors describe the evaluation of the NIL overlay performance using up-to-date NIL tools, and discuss the potentials of NIL overlay in the future. Alignment accuracy, precision, and overlay correction performance of NIL tools, NIL-to-NIL and NIL-to-optical lithography tool distortion matching performance and overlay error structure analysis, are discussed. From these analyses based on NIL overlay data, the authors discuss the possibility of NIL overlay evolution to realize the adaptation to mass production for the 1×-nm device.
Biologics in treating shoulder disease (2015)

Rotator cuff repair healing remains a significant clinical challenge despite technical advances in minimally invasive surgical repair. There is an unmet need for strategies to augment the repair construct by biologically enhancing the intrinsic healing potential of the tendon while mechanically protecting the healing enthesis during the immediate postoperative period. Platelet concentrates, scaffolds, and mesenchymal stem cells each hold promise for improving the healing rate and induce the regeneration of functional tissues. These strategies can enhance cell recruitment, proliferation, and differentiation, as well as provide a structural microenvironment for host cells through their three-dimensional configuration. Despite these potential benefits, there is currently limited clinical evidence supporting their efficacy in-vivo to improve structural healing rates and functional outcomes. Future work in this field is necessary to better understand the mechanism of action, appropriate indications, and favored methods of delivery for biological augments to tendon-bone healing.
Immunomodulatory properties of long‐term dietary supplementation with abscisic acid (2007)

Abscisic acid (ABA), a plant phytohormone, has been recently shown to be a natural PPAR γ agonist. Because other PPAR γ agonists elicit immunomodulatory properties, we sought to examine whether dietary ABA modulates phenotype and effector functions of T cell and macrophage subsets. C57BL6 mice were fed a basal AIN‐93G diet with 0 or 100 mg ABA/kg diet for 84 days. Following the dietary accumulation period, proliferation and cytokine production to anti‐CD3 stimulation were measured in splenocytes and mesenteric lymph node (MLN)‐derived lymphocytes. Mice fed ABA had significantly higher blastogenesis stimulation indices than control diet‐fed mice in the MLN, but not in the spleen. This was accompanied by an increase the percentage of CD4 + CD25 + cells following anti‐CD3 stimulation, increased interleukin‐10‐producing CD4 + CD25 + cells in the spleen and decreased interferon‐γ‐producing CD4 + CD25 − cells in both spleen and MLN. Previously, we have demonstrated that dietary ABA lowers the numbers of F4/80 + CD11b + CCR2 + macrophages infiltrating white adipose tissue. Consistent with our previous findings, ABA‐fed mice had lower percentages of macrophages in spleen and MLN. Collectively, these data suggest that dietary ABA‐supplementation diminishes T helper 1 responses and suppresses inflammation through a mechanism involving regulatory T cells.