gebhart/patrepeval huggingface dataset:
Detachably assembled microfluidic device for perfusion culture and post‐culture analysis of a spheroid array (2014)

Microfluidic devices permit perfusion culture of three-dimensional (3D) tissue, mimicking the flow of blood in vascularized 3D tissue in our body. Here, we report a microfluidic device composed of a two-part microfluidic chamber chip and multi-microwell array chip able to be disassembled at the culture endpoint. Within the microfluidic chamber, an array of 3D tissue aggregates (spheroids) can be formed and cultured under perfusion. Subsequently, detailed post-culture analysis of the spheroids collected from the disassembled device can be performed. This device facilitates uniform spheroid formation, growth analysis in a high-throughput format, controlled proliferation via perfusion flow rate, and post-culture analysis of spheroids. We used the device to culture spheroids of human hepatocellular carcinoma (HepG2) cells under two controlled perfusion flow rates. HepG2 spheroids exhibited greater cell growth at higher perfusion flow rates than at lower perfusion flow rates, and exhibited different metabolic activity and mRNA and protein expression under the different flow rate conditions. These results show the potential of perfusion culture to precisely control the culture environment in microfluidic devices. The construction of spheroid array chambers allows multiple culture conditions to be tested simultaneously, with potential applications in toxicity and drug screening.
Phospholipids of a Bone Matrix Calcification Nucleator (1978)

Phospholipids of a bone matrix calcification nucleator are identified as mono and diphosphoinositides and phosphatidyl serine. The nucleator, a protein-phospholipid complex, was dissociated by acidified-solvent porous-glass column chromatography. Analysis was by gas-liquid chromatography.
A decision-tree-based symbolic rule induction system for text categorization (2002)

We present a decision-tree-based symbolic rule induction system for categorizing text documents automatically. Our method for rule induction involves the novel combination of (1) a fast decision tree induction algorithm especially suited to text data and (2) a new method for converting a decision tree to a rule set that is simplified, but still logically equivalent to, the original tree. We report experimental results on the use of this system on some practical problems.
A Comparison of Guanosine-Quartet Inhibitory Effects Versus Cytidine Homopolymer Inhibitory Effects on Rat Neointimal Formation (1998)

Phosphorothioate oligodeoxynucleotides (PS oligos) manifest antisense and G-quartet aptameric inhibitory effects on vascular smooth muscle cell (SMC) proliferation. PS oligo cytidine homopolymers also have nonsequence-specific, non-G-quartet inhibitory effects on in vitro and in vivo SMC proliferation. In this study, we compared the effects of S-dC18 and S-dC28,18-mer and 28-mer cytidine homopolymers, respectively, which lack guanosines, with those of ZK10, a G-tetrad forming compound, on in vitro SMC proliferation and in vivo neointimal formation. ZK10 significantly inhibited in vitro human aortic SMC proliferation. At the same molar concentration, ZK10 had significantly greater inhibitory potency on SMC proliferation than either S-dC18, S-dC28, or 7DG-ZK10, which is a modified ZK10 with ten 7-deaza guanosine substitutions. ZK10 was significantly more potent than S-dC18 and S-dC28 in inhibiting PDGF-induced in vitro SMC migration. S-dC18, S-dC28, and ZK10 treatment significantly reduced the intima/media area ratio after rat carotid artery balloon injury compared with the values of the control groups. ZK10 was a more potent inhibitor of neointimal formation than the same chain length S-dC18. ZK10 formed higher-order structures, as shown on gel electrophoresis, in contrast to S-dC28 and 7DG-ZK10. Therefore, the 18-mer ZK10 has comparable in vivo SMC inhibitory effects to the 28-mer S-dC28, a fact that may have ramifications for the development of optimal PS oligos to inhibit angioplasty restenosis.
Target Enzyme Recognition by Calmodulin: 2.4 Å Structure of a Calmodulin-Peptide Complex (1992)

The crystal structure of calcium-bound calmodulin (Ca(2+)-CaM) bound to a peptide analog of the CaM-binding region of chicken smooth muscle myosin light chain kinase has been determined and refined to a resolution of 2.4 angstroms (A). The structure is compact and has the shape of an ellipsoid (axial ratio approximately 2:1). The bound CaM forms a tunnel diagonal to its long axis that engulfs the helical peptide, with the hydrophobic regions of CaM melded into a single area that closely covers the hydrophobic side of the peptide. There is a remarkably high pseudo-twofold symmetry between the closely associated domains. The central helix of the native CaM is unwound and expanded into a bend between residues 73 and 77. About 185 contacts (less than 4 A) are formed between CaM and the peptide, with van der Waals contacts comprising approximately 80% of this total.
Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives (2018)

The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS.
Hypoxia Prevents Induction of Aromatase Expression in Human Trophoblast Cells in Culture: Potential Inhibitory Role of the Hypoxia-Inducible Transcription Factor Mash-2 (Mammalian Achaete-Scute Homologous Protein-2) (2000)

The human placenta has a remarkable capacity to aromatize C19-steroids, produced by the fetal adrenals, to estrogens. This reaction is catalyzed by aromatase P450 (P450arom), encoded by the CYP19 gene. In placenta, CYP19 gene expression is restricted to the syncytiotrophoblast layer. Cytotrophoblasts isolated from human placenta, when placed in monolayer culture in 20% O2, spontaneously fuse to form syncytiotrophoblast. These morphological changes are associated with a marked induction of aromatase activity and CYP19 gene expression. When cytotrophoblasts are cultured in an atmosphere containing 2% O2, they manifest increased rates of DNA synthesis and fail to fuse and form syncytiotrophoblast. The objective of the present study was to utilize cytotrophoblasts isolated from midterm human placenta to analyze the effects of O2 on CYP19 gene expression and the molecular mechanisms that mediate these effects. We observed that when trophoblast cells were maintained in 2% O2, there was only a modest induction of CYP19 expression as a function of time in culture, and aromatase activity was barely detectable. However, when cytotrophoblasts that had been maintained in 2% O2 for 3 days were placed in a 20% O2 environment, there was a rapid onset of cell fusion and induction of P450arom mRNA and aromatase activity. In addition, mRNAs for the helix-loop-helix factors Mash-2 (mammalian achaete-scute homologous protein-2) and Id1 (inhibitor of differentiation 1) were readily detectable in freshly isolated cytotrophoblasts and were markedly decreased upon differentiation to syncytiotrophoblast in 20% O2. By contrast, when cytotrophoblasts were cultured in 2% O2, mRNA levels for Mash-2 and Id1 remained elevated. Interestingly, overexpression of Mash-2 in primary cultures of human trophoblast cells markedly inhibited cell fusion and the spontaneous induction of P450arom mRNA levels and caused a marked decrease in expression of co-transfected fusion gene constructs containing either 125, 201, 246, or 501 bp of DNA flanking the 5'-end of the placenta-specific exon (exon I.1) of the human CYP19 gene linked to the human GH (hGH) structural gene, as reporter. In studies using BeWo, a human choriocarcinoma cell line, overexpression of Mash-2 also inhibited expression of cotransfected CYP19I.1:hGH fusion gene constructs. The findings that Mash-2 had no effect on the expression of a CYP19I.1(-42):hGH fusion gene in primary cultures of human trophoblast and BeWo cells suggest that Mash-2 exerts its inhibitory effects directly or indirectly though CYP19I.1 5'-flanking sequences that lie between -42 and -125 bp. By contrast, neither Id1 nor Id2 had an effect on CYP19I. 1 promoter activity in the transfected BeWo cells. These findings suggest that Mash-2 may serve as a hypoxia-induced transcription factor that prevents differentiation to syncytiotrophoblast and aromatase induction in human trophoblast cultured under low O2 conditions.
Improved Lymphocyte Function-associated Antigen-1 (LFA-1) Inhibition by Statin Derivatives (2004)

The integrin lymphocyte function-associated antigen-1 (LFA-1) (alphaLbeta2; CD11a/CD18) plays an important role in leukocyte migration and T cell activation. LFA-1 is inhibited by the cholesterol-lowering drug lovastatin, which binds to an allosteric site of the alphaL I domain termed the lovastatin site (L-site). Here we report for the first time the x-ray structures of the LFA-1 I domain complexed with derivatives of lovastatin optimized for LFA-1 inhibition. This analysis identified two new subpockets within the L-site occupied by chemical groups of the statin derivatives but not by lovastatin itself. Occupancy of these L-site subpockets led to distinct conformational changes in LFA-1, which were detectable by an epitope-monitoring assay. We utilized this assay to demonstrate improved LFA-1 inhibition in human blood in vitro and in blood samples from treated animals ex vivo. Moreover, we demonstrate that the novel lovastatin-derived LFA-1 inhibitor LFA878 exhibits potent anti-inflammatory effects in carrageenan-induced rat paw edema. In summary, the findings reported here extend the understanding of LFA-1 inhibition at the molecular level, allow for the identification and design of LFA-1 inhibitors of further enhanced potency, and support the expectation that LFA-1 inhibitors binding to the L-site will be of therapeutic value in treating inflammatory diseases.
Propionibacterium freudenreichii component 1.4-dihydroxy-2-naphthoic acid (DHNA) attenuates dextran sodium sulphate induced colitis by modulation of bacterial flora and lymphocyte homing (2005)

DHNA, a novel type of prebiotic, attenuates colonic inflammation not only by balancing intestinal bacterial flora but also by suppressing lymphocyte infiltration through reduction of MAdCAM-1.
The effects of Yucca schidigera and Quillaja saponaria on growth performance and enzymes activities of juvenile shrimp Litopenaeus vannamei cultured in low salinity water (2016)

The inclusion of Yucca schidigera and Quillaja saponaria extracts (NTF) in aquatic organisms display a positive response on production and organism’s physiology. Fifteen tanks (140 L) with low-salinity water (S = 5) were stocked with 10 juvenile shrimp ( Litopenaeus vannamei , 2.6 g of mean weight) feeding with 0, 0.25, 0.5, 1.0 and 2.0 g kg -1 of NTF of basal diet (triplicate treatment). The shrimp were cultured in a close recirculation system (control condition) and fed ad libitum daily for 40 days. General growth parameters (body weight, growth, body length, feed conversion rate, survival) and hepatopancreatic digestive enzyme activities (alkaline protease, alkaline phosphatase, α-amylase, leucine aminopeptidase, and lipase) were evaluated after 40 days of shrimp culture. The final mean body weight, individual mean body, weight gain, and feed conversion ratio from shrimp feeding with 1.0 and 2.0 g kg -1 of NTF have a significant ( P &lt; 0.05) result compared to other treatments. The highest values of alkaline protease, lipase, and α-amylase were detected in shrimp feeding with 0.5 g kg -1 of NTF, where a high level of leucine aminopeptidase and alkaline phosphatase were detected with 0.25 g kg -1 of NTF treatment. However, any significant differences in enzyme activities were detected between the control group and treatments. The increase effect in shrimp growth and any decrease effect in enzyme activity detected in present study suggest that NTF shows potential as a feed additive for shrimp cultured at low-salinity.
The Gas6/Axl System (1999)

Signal transduction downstream of tyrosine kinases has become an increasingly important area of study in cardiovascular biology. In this review, we consider the experimental evidence pointing to significant roles for the Axl receptor tyrosine kinase and its ligand, Gas6, in the vasculature. An introduction to the Gas6/Axl system and a discussion of its discovery is followed by a summary of the data regarding expression of Gas6/Axl in injured arteries. We conclude by discussing mechanisms by which Gas6/Axl signaling may impact on the response of blood vessels to injury, thereby contributing to the development of atherosclerosis and/or restenosis.
Resource sharing in reservation-based systems (2005)

The resource-sharing problem in priority-driven realtime systems has been studied at length, with the result that some effective and practical solutions are available for both fixed-priority and dynamic-priority systems. In recent years, real-time operating systems have begun to support the resource reservation paradigm, providing a "temporal isolation" abstraction. However the problem of sharing logical resources across reserved applications has not been extensively studied. In this paper we consider both the theoretical and practical implications of such resource-sharing in reservation-based systems. Moreover we provide some experimental results from the implementation of our proposed schemes in Linux/RK, a "resource kernel" that supports reservations.
Learning from Labeled and Unlabeled Data with Label Propagation (2002)

We investigate the use of unlabeled data to help labeled data in classification. We propose a simple iterative algorithm, label propagation, to propagate labels through the dataset along high density areas defined by unlabeled data. We give the analysis of the algorithm, show its solution, and its connection to several other algorithms. We also show how to learn parameters by minimum spanning tree heuristic and entropy minimization, and the algorithm&amp;apos;s ability to do feature selection. Experiment results are promising.
Processing Complex Mixtures of Intact Proteins for Direct Analysis by Mass Spectrometry (2002)

For analysis of intact proteins by mass spectrometry (MS), a new twist to a two-dimensional approach to proteome fractionation employs an acid-labile detergent instead of sodium dodecyl sulfate during continuous-elution gel electrophoresis. Use of this acid-labile surfactant (ALS) facilitates subsequent reversed-phase liquid chromatography (RPLC) for a net two-dimensional fractionation illustrated by transforming thousands of intact proteins from Saccharomyces cerevisiae to mixtures of 5-20 components (all within approximately 5 kDa of one another) for presentation via electrospray ionization (ESI) to a Fourier transform MS (FTMS). Between 3 and 13 proteins have been detected directly using ESI-FTMS (or MALDI-TOF), and the fractionation showed a peak capacity of approximately 400 between 0 and 70 kDa. A probability-based identification was made automatically from raw MS/MS data (obtained using a quadrupole-FTMS hybrid instrument) for one protein that differed from that predicted in a yeast database of approximately 19,000 protein forms. This ALS-PAGE/RPLC approach to proteome processing ameliorates the "front end" problem that accompanies direct analysis of whole proteins and assists the future realization of protein identification with 100% sequence coverage in a high-throughput format.
HIV Entry Inhibitors Targeting gp41: From Polypeptides to Small-Molecule Compounds (2006)

HIV envelope glycoprotein transmembrane subunit gp41 plays a critical role in the fusion between viral and target cell membranes. Upon gp120 binding to CD4 and a coreceptor (CCR5 or CXCR4), gp41 changes its conformation by forming N-helix trimer between N-heptad repeats (NHRs) and then six-helix bundle between the N-trimer and the C-heptad repeats (CHRs). Peptides derived from the NHR and CHR of gp41 extracellular region have demonstrated potent inhibitory activity on the HIV mediated cell fusion. One of these peptides, T-20, became the first success of a new class of anti-HIV agents, named HIV entry inhibitors. However, a relatively long peptide such as T-20 suffers from several limitations including lack of oral bioavailability and high cost of production. Great efforts have been made to develop alternative peptides and proteins with improved anti-HIV-1 activity, increased bioavailability and reduced cost of production. The most promising approach is the development of small molecule HIV entry inhibitors targeting gp41. Any molecule that blocks the process of NHR homotrimerization and the six-helix bundle formation by targeting the gp41 NHR, NHR trimer and CHR may inhibit HIV-mediated membrane fusion. The progress in development of those anti-HIV agents targeting gp41, from polypeptides to small-molecule compounds, is reviewed.
Field, Laboratory, and Analytical Investigation of Angles-with-Plate Retrofit for Distortion-Induced Fatigue in Steel Bridges (2015)

Prior to the mid-1980s, steel girder bridges were designed with a detail susceptible to distortion-induced fatigue cracking. While a number of retrofit measures have been developed to repair this problem, many of those retrofits have long-term performance issues or are difficult and expensive to implement. Recent research at the University of Kansas has focused on the development of a new retrofit measure that could be effective in repairing distortion-induced fatigue cracking while also being inexpensive and easier to install than currently available retrofits. This new retrofit measure, referred to as the “angles-with-plate” retrofit, stiffens the problematic region and redistributes distortion-induced fatigue stresses away from cracking prone areas. By eliminating the need for cumbersome installation procedures, the angles-with-plate retrofit also provides a more economical repair that can be implemented with minimal traffic interruptions. This dissertation is presented in three parts and appendices. Part I provides a brief overview of distortion-induced fatigue cracking and the development of the angles-with-plate retrofit. Part II gives details and findings of an experimental investigation of the performance of the angles-with-plate retrofit and a stiffened version of the angles-with-plate retrofit on a 9.1 m (30 ft.) laboratory test bridge. Part III describes field and analytical tests performed on an active steel girder bridge system near Park City, Kansas on which the angles-with-plate retrofit was used as a repair for distortion-induced fatigue cracking.
Activity of B-Nor Analogues of Neurosteroids on the GABAAReceptor in Primary Neuronal Cultures (2006)

A GABA(A) receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-norallopregnanolone (i.e., 3alpha-hydroxy-7-nor-5alpha-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons in culture: this time, both 3alpha-hydroxy-7-nor-5xi-pregnan-20-ones (5 and 6) were found to stimulate [3H]flunitrazepam binding and GABA-induced 36Cl- influx. These effects were inhibited by GABA(A) receptor antagonists. Other analogues carrying electronegative substituents (epoxides 9 and 10 and ketone 12) in the B ring were inactive. Similarly, B-normal ketones 17, and 18 and 6-azasteroids 20 and 21 were also inactive. B-Nor analogues 5 and 6 did not induce neurotoxicity at relevant concentrations. A computational analysis of active and inactive neurosteroid analogues allowed the proposal of a 3D pharmacophoric hypothesis of their interaction with the GABA(A) receptor.
Sparse image coding using a 3D non-negative tensor factorization (2005)

We introduce an algorithm for a non-negative 3D tensor factorization for the purpose of establishing a local parts feature decomposition from an object class of images. In the past, such a decomposition was obtained using non-negative matrix factorization (NMF) where images were vectorized before being factored by NMF. A tensor factorization (NTF) on the other hand preserves the 2D representations of images and provides a unique factorization (unlike NMF which is not unique). The resulting "factors" from the NTF factorization are both sparse (like with NMF) but also separable allowing efficient convolution with the test image. Results show a superior decomposition to what an NMF can provide on all fronts - degree of sparsity, lack of ghost residue due to invariant parts and efficiency of coding of around an order of magnitude better. Experiments on using the local parts decomposition for face detection using SVM and Adaboost classifiers demonstrate that the recovered features are discriminatory and highly effective for classification.
Analysis of Heat-Shock Transcription Factor and Element-Binding Activity (2003)

Stress response is nearly universal. Living organisms respond to the changes in their chemical, physical, and biological environments by synthesizing a group of proteins called stress or heat-shock proteins (). The preferential synthesis of these proteins appears to be involved in induced transient thermal resistance (). It is well known that transcription of heat-shock genes is regulated by heat-shock transcription factors (HSFs), which bind to heat-shock elements (HSEs) located in the promoter region of genes encoding heat-shock proteins (). Heat-shock protein gene promoter contains three heat-shock elements (HSE, 5′-GAAnnTTCnnGAA-3′) (). The HSE is known as a conserved motif present in the promoters of many heat-inducible heat-shock protein genes. Many studies have demonstrated that stress-induced denatured, unfolded, or malfolded proteins trigger the activation of heat shock transcription factors (HSFs) (, , ). In mammalian cells, the activated HSF binds to the HSE and then stimulates transcription.
Benevolent Institutions and Their Lady Managers (1997)

Abstract This chapter focuses on the women's benevolent institutions. They were in place in 1880 dispensing aid on a regular basis. By ministering the poor, benevolent ladies understood the degree of dependency that was created through increased industrialization and growth. Catholic women's religious orders were the first to build benevolent institutions in Galveston. Ursuline nuns accompanied Bishop John Mary Odin to Galveston and formed the Ursuline Academy and convent. They acted as nurses. They converted their convent to a military hospital during the Civil War. Galveston's middle- and upper-class women sought to capitalize on the wave of pride and donation to build institutions of their own — for children and old women. Lasker Home for Homeless Children and the Johanna Runge Free Kindergarten pulled women toward a greater sense of civic and community responsibility. These institutions were temporary shelters for children whose family was unable to offer an education.