gebhart/patrepeval huggingface dataset:
The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy (2007)

For the last four decades, the treatment of cancer has relied on four treatment modalities, namely surgery, radiotherapy, cytotoxic chemotherapy, and hormonotherapy. Most of these therapies are believed to directly attack and eradicate tumor cells. The emerging concept that cancer is not just a disease of a tissue or an organ but also a host disease relies on evidence of tumor-induced immunosuppression and polymorphisms in genes involved in host protection against tumors. This theory is now gaining new impetus, based on our recent data showing that optimal therapeutic effects require the immunoadjuvant effect of tumor cell death induced by cytotoxic anticancer agents. Here, we show that the release of the high mobility group box 1 protein (HMGB1) by dying tumor cells is mandatory to license host dendritic cells (DCs) to process and present tumor antigens. HMGB1 interacts with Toll-like receptor 4 (TLR4) on DCs, which are selectively involved in the cross-priming of anti-tumor T lymphocytes in vivo. A TLR4 polymorphism that affects the binding of HMGB1 to TLR4 predicts early relapse after anthracycline-based chemotherapy in breast cancer patients. This knowledge may be clinically exploited to predict the immunogenicity and hence the efficacy of chemotherapeutic regimens.
Molecular dynamics and multiscale homogenization analysis of seepage/diffusion problem in bentonite clay (2002)

Abstract A scheme combining a molecular behaviour and macro‐continuum phenomenon is presented for bentonite clay, which is a key component of a barrier system for disposal and containment of hazardous wastes. On designing a disposal facility we use a macro‐phenomenological model. However the existing model is not sufficiently effective. Bentonite is a microinhomogeneous material. Properties of the saturated bentonite are characterized by montmorillonite and water, called montmorillonite hydrate. Since the crystalline structure of montmorillonite determines the fundamental properties of the montmorillonite hydrate, we analyse its molecular behaviour by applying a molecular dynamics simulation to enquire into the physicochemical properties of the montmorillonite hydrate such as diffusivity of chemical species. For extending the microscopic characteristics of constituent materials to a macroscopic diffusion behaviour of the microinhomogeneous material we apply a multiscale homogenization analysis, especially in order to treat micro‐level of adsorption behaviour. Copyright © 2002 John Wiley &amp; Sons, Ltd.
Polarized Raman Spectroscopy on Isolated Single-Wall Carbon Nanotubes (2000)

Polarized micro-Raman spectroscopy has been performed on spatially separated single-wall carbon nanotubes (SWNTs) in the form of individual nanotubes or thin ropes of only a few SWNTs. Different from bulk samples, the Raman spectra are composed of well-resolved peaks which allow a direct comparison of experimental data with theoretical calculations. Orientation-dependent measurements reveal maximum intensity of all Raman modes when the nanotubes are aligned parallel to the polarization of the incident laser light. The angular dependences clearly deviate from the selection rules predicted by theoretical studies. These differences are attributed to depolarization effects caused by the strongly anisotropic geometry of the nanotubes and to electronic resonance effects for excitation at 633 nm.
2 .ANG. Resolution Structure of DppA, a Periplasmic Dipeptide Transport/Chemosensory Receptor (1995)

The family of about 50 periplasmic binding proteins, which exhibit diverse specificity (e.g., carbohydrates, amino acids, dipeptides, oligopeptides, oxyanions, metals, and vitamins) and range in size from 20 to 58 kDa, is a gold mine for an atomic-level investigation of structure and molecular recognition. These proteins serve as initial receptors for active transport systems or permeases. About six of these proteins, including the dipeptide-binding protein (DppA), are also primary receptors for chemotaxis. The structure of the unbound form of DppA (M(r) = 57,400) has been determined and refined to an R-factor of 0.169 to 2 A resolution. DppA consists of two distinct domains (I and II) connected by two "hinge" segments which form part of the base of the wide groove between the two domains. The relative orientation of the two domains gives the protein a pearlike shape, with domain I and domain II forming the larger and smaller apical ends, respectively. From the tip to the rounded bottom measures about 85 A, and the widest diameter is about 60 A. Domain I, which consists of two integrated subdomains, is folded from two separate polypeptide segments from the amino- and carboxyl-terminal ends. The more compact domain II is formed from the intervening segment. Comparison of the dipeptide-binding protein structure with that of the bound form of the similar oligopeptide-binding protein [Tame, J. R. H., Murshudov, G. N., Dodson, E. J., Neil, T. K., Dodson, G. G., Higgins, C. F., & Wilkinson, A. J. (1994) Science 264, 1578-1581] reveals the major features that differentiate the ligand specificity of the two proteins and describe the large hinge bending (about 55 degrees) between the two domains.
Chemical sensors based on molecularly modified metallic nanoparticles (2007)

This paper presents a concise, although admittedly non-exhaustive, didactic review of some of the main concepts and approaches related to the use of molecularly modified metal nanoparticles in or as chemical sensors. This paper attempts to pull together different views and terminologies used in sensors based on molecularly modified metal nanoparticles, including those established upon electrochemical, optical, surface Plasmon resonance, piezoelectric and electrical transduction approaches. Finally, this paper discusses briefly the main advantages and disadvantages of each of the presented class of sensors.
Efficient and Non-Convex Coordinate Descent for Symmetric Nonnegative Matrix Factorization (2016)

Given a symmetric nonnegative matrix A, symmetric nonnegative matrix factorization (symNMF) is the problem of finding a nonnegative matrix H, usually with much fewer columns than A, such that A ≈ HH <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sup> . SymNMF can be used for data analysis and in particular for various clustering tasks. Unlike standard NMF, which is traditionally solved by a series of quadratic (convex) subproblems, we propose to solve symNMF by directly solving the nonconvex problem, namely, minimize ∥A - HH <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sup> ∥ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , which is a fourth-order nonconvex problem. In this paper, we propose simple and very efficient coordinate descent schemes, which solve a series of fourth-order univariate subproblems exactly. We also derive convergence guarantees for our methods and show that they perform favorably compared to recent state-of-the-art methods on synthetic and real-world datasets, especially on large and sparse input matrices.
Effects of natalizumab, an α4 integrin inhibitor, on fertility in male and female guinea pigs (2009)

Natalizumab had no effects on male fertility, but did result in a reduction in pregnancy rates in females treated with the high dose of 30 mg/kg.
Nerve growth factor protein level increases in the adult rat hippocampus aftera specific cholinergic lesion (1987)

Nerve growth factor (NGF) is the best-characterized neurotrophic substance and has recently been shown to influence cholinergic neurons in the basal forebrain. Hippocampus and neocortex, the primary targets for these central neurons, have further been found to contain high levels of NGF. Using enzyme immunoassay and acetylcholine esterase (AChE) histochemistry we have now studied the levels of NGF and AChE after a specific cholinergic lesion, transection of the fimbria fornix comprising the major cholinergic input to hippocampus. Fimbriectomy in adult rats led to a marked decrease in AChE-positive nerve terminals in both hippocampus and neocortex 10 days later, and to an increase (40%) of NGF protein concentration in hippocampus. thirty days after surgery, NGF had returned to control levels and remained there after 90 days. Removal of superior cervical ganglion did not alter the results. The density of cholinergic terminals in both hippocampus and neocortex increased with time (90 days) after fimbrial transection. The results support the idea that cholinergic neurons in the basal forebrain take up and retrogradely transport NGF from their target areas and suggest that transection of the pathway interrupts the transport thereby increasing NGF distal to the lesion. The return of NGF to control levels probably reflects reestablished cholinergic contracts in the hippocampus.
Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. (2000)

We report here the use of viral fusogenic membrane glycoproteins (FMGs) as a new class of therapeutic genes for the control of tumor growth. FMGs kill cells by fusing them into large multinucleated syncytia, which die by sequestration of cell nuclei and subsequent nuclear fusion by a mechanism that is nonapoptotic, as assessed by multiple criteria. Direct and bystander killing of three different FMGs were at least one log more potent than that of herpes simplex virus thymidine kinase or cytosine deaminase suicide genes. Transduction of human tumor xenografts with plasmid DNA prevented tumor outgrowth in vivo, and cytotoxicity could be regulated through transcriptional targeting. Syncytial formation is accompanied by the induction of immunostimulatory heat shock proteins, and tumor-associated FMG expression in immunocompetent animals generated specific antitumor immunity.
The impact of hyaluronic acid oligomer content on physical, mechanical, and biologic properties of divinyl sulfone‐crosslinked hyaluronic acid hydrogels (2010)

In recent studies, we showed that exogenous hyaluronic acid oligomers (HA-o) stimulate functional endothelialization, though native long-chain HA is more bioinert and possibly more biocompatible. Thus, in this study, hydrogels containing high molecular weight (HMW) HA (1 x 10(6) Da) and HA-o mixtures (HA-o: 0.75-10 kDa) were created by crosslinking with divinyl sulfone (DVS). The incorporation of HA-o was found to compromise the physical and mechanical properties of the gels (rheology, apparent crosslinking density, swelling ratio, degradation) and to very mildly enhance inflammatory cell recruitment in vivo; increasing the DVS crosslinker content within the gels in general, had the opposite effect, though the relatively high concentration of DVS within these gels (necessary to create a solid gel) also stimulated a mild subcutaneous inflammatory response in vivo and VCAM-1 expression by endothelial cells (ECs) cultured atop; ICAM-expression levels remained very low irrespective extent of DVS crosslinking or HA-o content. The greatest EC attachment and proliferation (MTT assay) was observed on gels that contained the highest amount of HA-o. The study shows that the beneficial EC response to HA-o and biocompatibility of HA is mostly unaltered by their chemical derivatization and crosslinking into a hydrogel. However, the study also demonstrates that the relatively high concentrations of DVS, necessary to create solid gels, compromise their biocompatibility. Moreover, the poor mechanics of even these heavily crosslinked gels, in the context of vascular implantation, necessitates the investigation of other, more appropriate crosslinking agents. Alternately, the outcomes of this study may be used to guide an approach based on chemical immobilization and controlled surface-presentation of both bioactive HA-o and more biocompatible HMW HA on synthetic or tissue engineered grafts already in use, without the use of a crosslinker, so that improved, predictable, and functional endothelialization can be achieved, and the need to create a mechanically compliant biomaterial for standalone use, circumvented.
Less is More: Active Learning with Support Vector Machines (2000)

We describe a simple active learning heuristic which greatly enhances the generalization behavior of support vector machines (SVMs) on several practical document classification tasks. We observe a number of benefits, the most surprising of which is that a SVM trained on a wellchosen subset of the available corpus frequently performs better than one trained on all available data. The heuristic for choosing this subset is simple to compute, and makes no use of information about the test set. Given that the training time of SVMs depends heavily on the training set size, our heuristic not only offers better performance with fewer data, it frequently does so in less time than the naive approach of training on all available data. 1. Introduction There are many uses for a good document classifier --- sorting mail into mailboxes, filtering spam or routing news articles. The problem is that learning to classify documents requires manually labelling more documents than a typical...
Time-domain optical sensing (1999)

A chirped optical supercontinuum is used to map absorption spectra into temporal waveforms. Time-domain spectral measurement of acetylene is demonstrated using a modelocked fibre laser as the source of broadband radiation and a sampling oscilloscope for spectral measurement.
l-Citrulline ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets (2009)

Newborn piglets develop pulmonary hypertension and have diminished pulmonary vascular nitric oxide (NO) production when exposed to chronic hypoxia. NO is produced by endothelial NO synthase (eNOS) in the pulmonary vascular endothelium using l-arginine as a substrate and producing l-citrulline as a byproduct. l-Citrulline is metabolized to l-arginine by two enzymes that are colocated with eNOS in pulmonary vascular endothelial cells. The purpose of this study was to determine whether oral supplementation with l-citrulline during exposure of newborn piglets to 10 days of chronic hypoxia would prevent the development of pulmonary hypertension and increase pulmonary NO production. A total of 17 hypoxic and 17 normoxic control piglets were studied. Six of the 17 hypoxic piglets were supplemented with oral l-citrulline starting on the first day of hypoxia. l-Citrulline supplementation was provided orally twice a day. After 10 days of hypoxia or normoxia, the animals were anesthetized, hemodynamic measurements were performed, and the lungs were perfused in situ. Pulmonary arterial pressure and pulmonary vascular resistance were significantly lower in hypoxic animals treated with l-citrulline compared with untreated hypoxic animals (P < 0.001). In vivo exhaled NO production (P = 0.03) and nitrite/nitrate accumulation in the perfusate of isolated lungs (P = 0.04) were significantly higher in l-citrulline-treated hypoxic animals compared with untreated hypoxic animals. l-Citrulline supplementation ameliorated the development of pulmonary hypertension and increased NO production in piglets exposed to chronic hypoxia. We speculate that l-citrulline may benefit neonates exposed to prolonged periods of hypoxia from cardiac or pulmonary causes.
Gastrointestinal Transit and Release of Mesalazine Tablets in Patients with Inflammatory Bowel Disease (1990)

Gastrointestinal transit and release of a delayed-release, enteric-coated tablet of mesalazine (Claversal) were studied in 13 patients with Crohn's disease and ulcerative colitis. The tablets disintegrated a mean of 3.2 h after leaving the stomach, resulting in drug dispersion in the distal small intestine or proximal colon. Tablet disintegration closely correlated with onset of drug absorption. Peak mean concentrations of mesalazine and its main metabolite, Ac-5-ASA, were 0.5 microgram/ml and 1.0 microgram/ml, respectively, and occurred 3 to 4 h after gastric emptying. The plasma levels correlated with scintigraph images of tablet disintegration. It is concluded that the tablets effectively deliver mesalazine to the terminal ileum and proximal colon in patients with inflammatory bowel disease.
P‐glycoprotein inhibition promotes prednisone retention in human sinonasal polyp explants (2014)

Background P‐glycoprotein (P‐gp) is an efflux pump, which is part of the innate chemo‐immunity defense system and is overexpressed in chronic rhinosinusitis with nasal polyps (CRSwNP). P‐gp is capable of regulating corticosteroid retention and thus P‐gp upregulation has been implicated in steroid resistance in several inflammatory disorders. The goal of this study is to determine whether P‐gp regulates intracellular steroid retention in CRSwNP. Methods This was a Massachusetts Eye and Ear Infirmary Institutional Review Board (IRB)‐approved study in nasal polyp explants. Polyps were exposed to 50 μg/mL of prednisone for 30 minutes with or without the presence of a P‐gp inhibitor (Verapamil 12.5 μM or Zosuquidar 0.31 μM) followed by a 40‐minute washout period (n = 16 per group). Intracellular steroid retention was determined by quantifying the concentration of both intracytoplasmic and secreted steroid using an enzyme‐linked immunosorbent assay (ELISA). Concentrations relative to control were compared using a Student t test. Results The intracytoplasmic prednisone concentration was significantly greater relative to control following P‐gp inhibition with Verapamil (155.28% ± 22.48%, p &lt; 0.05) and Zosuquidar (125.81% ± 12.41%, p &lt; 0.05). Similarly, the amount of prednisone secreted by the explant was significantly reduced at 30 minutes following P‐gp inhibition with Zosuquidar (78.64% ± 2.98%, p &lt; 0.05) and 40 minutes following P‐gp inhibition with Verapamil (80.56% ± 5.02%, p &lt; 0.05). Conclusion Inhibition of P‐gp enhances the intracellular accumulation of prednisone in nasal polyps. This suggests that P‐gp participates in regulation of glucocorticoid retention in sinonasal mucosa. These findings, coupled with the known overexpression of P‐gp in CRSwNP, may point to a possible mechanism for steroid resistance in this patient population.
Human Marrow-Derived Mesenchymal Stem Cells (MSCs) Express Hematopoietic Cytokines and Support Long-Term Hematopoiesis When Differentiated Toward Stromal and Osteogenic Lineages (2000)

Human mesenchymal stem cells (MSCs), bone marrow-derived pluripotent adherent cells of mesenchymal origin can differentiate along the osteogenic, chondrogenic, adipogenic, and tendonogenic lineages. In this report we characterize cytokine and growth factor gene expression by MSCs and investigate the modulation of cytokine expression that occurs during osteogenic and stromal differentiation. MSCs constitutively expressed mRNA for interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), and stem cell factor (SCF). MSCs treated with IL-1alpha upregulated mRNA levels of IL-6, IL-11, and LIF, and began to express detectable levels of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF). mRNA levels of M-CSF and SCF did not change. MSCs cultured in osteogenic medium differentiated along the osteogenic lineage and downregulated mRNA levels of IL-6, IL-11 and LIF whereas, M-CSF and SCF expression were unchanged and G-CSF and GM-CSF remained undetectable. IL-3 was not detected in MSC culture under any conditions. MSCs precultured in control medium, IL-1alpha, or osteogenic medium maintained similar capacity to support long-term culture initiating cell (LT-CIC). Thus, primary and osteogenic differentiated MSCs produce important hematopoietic cytokines and support hematopoiesis in long-term cultures, suggesting that these cells may provide an excellent ex vivo environment for hematopoiesis during progenitor cell expansion and may be important for in vivo cell therapy.
Therapeutic Applications Of Oligonucleotides (1992)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Elicitation of structure-specific antibodies by epitope scaffolds (2010)

Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context has been a challenge for vaccine design. Here we demonstrate the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope of the broadly neutralizing antibody 2F5. This conformationally flexible region of gp41 assumes mostly helical conformations but adopts a kinked, extended structure when bound by antibody 2F5. Computational techniques were employed to transplant the 2F5 epitope into select acceptor scaffolds. The resultant "2F5-epitope scaffolds" possessed nanomolar affinity for antibody 2F5 and a range of epitope flexibilities and antigenic specificities. Crystallographic characterization of the epitope scaffold with highest affinity and antigenic discrimination confirmed good to near perfect attainment of the target conformation for the gp41 molecular graft in free and 2F5-bound states, respectively. Animals immunized with 2F5-epitope scaffolds showed levels of graft-specific immune responses that correlated with graft flexibility (p < 0.04), while antibody responses against the graft-as dissected residue-by-residue with alanine substitutions-resembled more closely those of 2F5 than sera elicited with flexible or cyclized peptides, a resemblance heightened by heterologous prime-boost. Lastly, crystal structures of a gp41 peptide in complex with monoclonal antibodies elicited by the 2F5-epitope scaffolds revealed that the elicited antibodies induce gp41 to assume its 2F5-recognized shape. Epitope scaffolds thus provide a means to elicit antibodies that recognize a predetermined target shape and sequence, even if that shape is transient in nature, and a means by which to dissect factors influencing such elicitation.
Overexpression, purification, crystallization and data collection of 3-methylaspartase fromClostridium tetanomorphum (2001)

3-Methylaspartase (E.C. 4.3.1.2) catalyses the reversible anti elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to give mesaconic acid as well as a slower syn elimination from the (2S,3R)-epimer, L-erythro-3-methylaspartic acid. The anti-elimination reaction occurs in the second step of the catabolic pathway for glutamic acid in Clostridium tetanomorphum. The reverse reaction is of particular interest because the addition of ammonia to substituted fumaric acids is highly stereoselective and gives highly functionalized amino acids. The mechanism of the transformation is unusual and of considerable interest. 3-Methylaspartase from C. tetanomorphum has been overexpressed and purified from Escherichia coli. Crystals of the enzyme have been obtained by sitting-drop vapour diffusion. Two native data sets have been collected, one in-house on a rotating-anode generator to 3.2 A and one at the European Synchrotron Radiation Facility to 2.0 A. A 2.1 A data set has been collected on a crystal of selenomethionine protein. Combining the data sets identify the space group as P2(1)2(1)2, with unit-cell parameters a = 110.3, b = 109.9, c = 67.2 A, alpha = beta = gamma = 90 degrees. The asymmetric unit contains two monomers with 42% solvent. A self-rotation function indicates the presence of a twofold axis, consistent with a biological dimer.
Evaluation of inflammatory parameters in physical urticarias and effects of an anti‐inflammatory/antiallergic treatment (2002)

These results confirm the therapeutical value of treatment with nimesulide and ketotifen in PU and suggest that these agents are able to reduce the release and the expression of some inflammatory molecules that are up-regulated in PU.