gebhart/patrepeval huggingface dataset:
Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury * (2007)

Objective: To identify biological and clinical predictors of acute kidney injury in subjects with acute lung injury. Design: Secondary data analysis from a multicenter, randomized clinical trial. Setting: Intensive care units in ten university medical centers. Patients: A total of 876 patients enrolled in the first National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial. Interventions: Study subjects were randomized to receive a low tidal volume ventilation strategy and pharmacologic therapy with ketoconazole or lisofylline in a factorial design. Measurements and Main Results: We tested the association of baseline levels of interleukin-6, interleukin-8, interleukin-10, von Willebrand factor, tumor necrosis factor-[alpha], type I and II soluble tumor necrosis factor receptors (sTNFR-I and -II), protein C, plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney injury. Of 876 study participants who did not have end-stage renal disease, 209 (24%) developed acute kidney injury, defined as a rise in serum creatinine of >50% from baseline over the first four study days. The 180-day mortality rate for subjects with acute kidney injury was 58%, compared with 28% in those without acute kidney injury (p< .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1 levels were independently associated with acute kidney injury after adjustment for demographics, interventions, and severity of illness. A combination of clinical and biological predictors had the best area under the receiver operating characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was highly significant (p= .0003). Conclusions: Elevations in PAI-1, interleukin-6, and the sTNFRs in subjects with acute kidney injury suggest that disordered coagulation, inflammation, and neutrophil–endothelial interactions play important roles in the pathogenesis of acute kidney injury. The combination of these biological and clinical risk factors may have important and additive value in predictive models for acute kidney injury.
Synthesis and Ethylene Polymerization Activity of a Novel, Highly Active Single-Component Binuclear Neutral Nickel(II) Catalyst (2005)

The novel binuclear neutral nickel(II) complex [((2,6-iPr2C6H3)NCH)C6H3ONi(PPh3)Ph]2 (5), based on the 3,3‘-bisalicylaldimine ligand, has been synthesized in high yield, and its structure has been confirmed by X-ray crystallography, elemental analysis, and 1H NMR and 13C NMR spectra. Used in the polymerization of ethylene as an active single-component catalyst, the complex exhibited a high catalytic activity of up to 4.55 × 105 g of PE/((mol of Ni) h), and polyethylenes with a weight-average molecular weight (M̄w) of up to 487.7 kg/mol and relatively broad molecular weight distribution (M̄w/M̄n = 2.8−3.8) were produced.
An alternative leukocyte homotypic adhesion mechanism, LFA-1/ICAM-1-independent, triggered through the human VLA-4 integrin. (1990)

The VLA-4 (CD49d/CD29) integrin is the only member of the VLA family expressed by resting lymphoid cells that has been involved in cell-cell adhesive interactions. We here describe the triggering of homotypic cell aggregation of peripheral blood T lymphocytes and myelomonocytic cells by mAbs specific for certain epitopes of the human VLA alpha 4 subunit. This anti-VLA-4-induced cell adhesion is isotype and Fc independent. Similar to phorbol ester-induced homotypic adhesion, cell aggregation triggered through VLA-4 requires the presence of divalent cations, integrity of cytoskeleton and active metabolism. However, both adhesion phenomena differed at their kinetics and temperature requirements. Moreover, cell adhesion triggered through VLA-4 cannot be inhibited by cell preincubation with anti-LFA-1 alpha (CD11a), LFA-1 beta (CD18), or ICAM-1 (CD54) mAb as opposed to that mediated by phorbol esters, indicating that it is a LFA-1/ICAM-1 independent process. Antibodies specific for CD2 or LFA-3 (CD58) did not affect the VLA-4-mediated cell adhesion. The ability to inhibit this aggregation by other anti-VLA-4-specific antibodies recognizing epitopes on either the VLA alpha 4 (CD49d) or beta (CD29) chains suggests that VLA-4 is directly involved in the adhesion process. Furthermore, the simultaneous binding of a pair of aggregation-inducing mAbs specific for distinct antigenic sites on the alpha 4 chain resulted in the abrogation of cell aggregation. These results indicate that VLA-4-mediated aggregation may constitute a novel leukocyte adhesion pathway.
A system for wireless intra-ocular pressure measurements using a silicon micromachined sensor (1992)

A system for the continuous monitoring of intra-ocular pressure is described. The sensor is intended for permanent implantation, integrated with an artificial lens. The system consists of a capacitive pressure sensor, determining the resonance frequency of a passive LC network, and a detector, based on the grid-dip technique. The passive pressure sensing element is micromachined from two silicon wafers and connected to a gold-wire coil. Prototype sensors have been evaluated experimentally in vitro. Pressure has been measured remotely, with promising results.
A functional epitope on P-selectin that supports binding of P-selectin to P-selectin glycoprotein ligand-1 but not to sialyl Lewis X oligosaccharides (1998)

P-selectin mediates the adhesion of leukocytes to activated platelets and endothelial cells. To characterize the functional domains of P-selectin for ligand recognition, we established nine hybridoma cell lines secreting anti-rat P-selectin mAb. Among them, the mAb C215 bound both rat and human P-selectins, and inhibited binding of rat and human P-selectins to P-selectin glycoprotein ligand-1 (PSGL-1) from HL-60 cells. In contrast, mAb C215 failed to inhibit the binding of rat and human P-selectin-IgG to sialyl Lewis X (sLe(x)) oligosaccharides. Epitope mapping of mAb C215 using synthetic decapeptides revealed that mAb C215 binds specifically to an eight-residue epitope that spans amino acids 76-83 of rat P-selectin, a region completely conserved by human P-selectin. Synthetic peptides containing the mAb C215 epitope inhibited binding of P-selectin to PSGL-1, but not to sLe(x) oligosaccharides, suggesting that the C215 epitope on P-selectin may directly interact with a particular site on the PSGL-1 core protein essential for interaction with P-selectin, such as sulfated tyrosine residues. Our results suggest the presence of two ligand recognition sites on P-selectin necessary for binding to PSGL-1--one recognizes sLe(x), while the other recognises the PSGL-1 core protein.
The Basis for a Second-generation Highly Cross-linked UHMWPE (2006)

Highly cross-linked ultra-high molecular weight polyethylene (UHMWPE) decreases wear at the hip by more than 50% compared with conventional UHMWPE. However, melted highly cross-linked polyethylene may be susceptible to fatigue cracking, and annealed highly cross-linked polyethylene may be susceptible to in vivo oxidation. The second-generation highly cross-linked UHMWPE (X3 HXPE) uses a sequential irradiation and annealing process. It preserves mechanical strength properties and has the highest survivorship in functional fatigue testing. The free radical content is low, and its performance under accelerated aging is the same as virgin UHMWPE. Hip simulator studies with 32-mm acetabular components demonstrated 97% wear reduction compared with conventional UHMWPE, and 62% compared with a clinically successful first-generation annealed highly cross-linked polyethylene. The crystallinity, density, and tensile strength of the X3 HXPE material was unchanged by oxidative challenge. X3 HXPE material articulating on cobalt-chromium alloy yields a volumetric wear rate very similar to that of metal-on-metal articulations, but eliminates the concerns of metal ion release. Wear particles generated from the X3 HXPE were the same size as those produced from conventional UHMWPE. Preliminary results suggest X3 HXPE can be used for cups larger than 36 mm.
Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides (1987)

Lipids in fresh human milk do not inactivate viruses but become antiviral after storage of the milk for a few days at 4 or 23 degrees C. The appearance of antiviral activity depends on active milk lipases and correlates with the release of free fatty acids in the milk. A number of fatty acids which are normal components of milk lipids were tested against enveloped viruses, i.e., vesicular stomatitis virus, herpes simplex virus, and visna virus, and against a nonenveloped virus, poliovirus. Short-chain and long-chain saturated fatty acids had no or a very small antiviral effect at the highest concentrations tested. Medium-chain saturated and long-chain unsaturated fatty acids, on the other hand, were all highly active against the enveloped viruses, although the fatty acid concentration required for maximum viral inactivation varied by as much as 20-fold. Monoglycerides of these fatty acids were also highly antiviral, in some instances at a concentration 10 times lower than that of the free fatty acids. None of the fatty acids inactivated poliovirus. Antiviral fatty acids were found to affect the viral envelope, causing leakage and at higher concentrations, a complete disintegration of the envelope and the viral particles. They also caused disintegration of the plasma membranes of tissue culture cells resulting in cell lysis and death. The same phenomenon occurred in cell cultures incubated with stored antiviral human milk. The antimicrobial effect of human milk lipids in vitro is therefore most likely caused by disintegration of cellular and viral membranes by fatty acids. Studies are needed to establish whether human milk lipids have an antimicrobial effect in the stomach and intestines of infants and to determine what role, if any, they play in protecting infants against gastrointestinal infections.
Predicting Protein Function by Genomic Context: Quantitative Evaluation and Qualitative Inferences (2000)

Various new methods have been proposed to predict functional interactions between proteins based on the genomic context of their genes. The types of genomic context that they use are Type I: the fusion of genes; Type II: the conservation of gene-order or co-occurrence of genes in potential operons; and Type III: the co-occurrence of genes across genomes (phylogenetic profiles). Here we compare these types for their coverage, their correlations with various types of functional interaction, and their overlap with homology-based function assignment. We apply the methods to Mycoplasma genitalium, the standard benchmarking genome in computational and experimental genomics. Quantitatively, conservation of gene order is the technique with the highest coverage, applying to 37% of the genes. By combining gene order conservation with gene fusion (6%), the co-occurrence of genes in operons in absence of gene order conservation (8%), and the co-occurrence of genes across genomes (11%), significant context information can be obtained for 50% of the genes (the categories overlap). Qualitatively, we observe that the functional interactions between genes are stronger as the requirements for physical neighborhood on the genome are more stringent, while the fraction of potential false positives decreases. Moreover, only in cases in which gene order is conserved in a substantial fraction of the genomes, in this case six out of twenty-five, does a single type of functional interaction (physical interaction) clearly dominate (>80%). In other cases, complementary function information from homology searches, which is available for most of the genes with significant genomic context, is essential to predict the type of interaction. Using a combination of genomic context and homology searches, new functional features can be predicted for 10% of M. genitalium genes.
Differential effects of type I IFNs on the growth of WC1- CD8+ gamma delta T cells and WC1+ CD8- gamma delta T cells in vitro. (1999)

Type I IFNs have a broad array of immunoregulatory functions that include up-regulation of type 1 immune responses through enhancing differentiation and activation of CD8+ T cells and CD4+ Th1 cells. Ovine trophoblast IFN-tau is a recently described type I IFN with the potential for therapeutic use, based on its potent antiviral activity yet low toxicity. Studies were designed to determine the immunoregulatory effects of IFN-tau on Ag-stimulated T cells, and a novel effect of type I IFNs on gammadelta T cells was observed. In cultures of parasite Ag-stimulated bovine T cells that contained a mixture of alphabeta and gammadelta T cells, both IFN-tau and IFN-alpha suppressed the expansion of WC1+ CD2- CD6- CD8- gammadelta T cells, yet stimulated the growth of WC1- CD2+ CD6+ CD8+ gammadelta T cells and CD8+ alphabeta T cells. The CD8+ gammadelta T cell subset expressed high levels of the IL-2R alpha-chain. Furthermore, we showed that type I IFN enhanced IL-2 production by these Ag-stimulated T cell lines. In short term cultures of PBMC, IL-2 stimulated an expansion of WC1- CD6+ CD8+ gammadelta T cells, which was significantly increased by IFN-tau, even though IFN-tau alone did not support cell survival. These studies demonstrate for the first time that type I IFNs differentially modulate the proliferation of different subsets of gammadelta T cells, which appears to act in part via IL-2.
On the Computation of Convolution in Actuarial Problems. Some Further Results (2005)

In questo lavoro vengono presentati ulteriori risultati in merito all’applicazione del metodo FDC (Fast Direct Convolution). Questo metodo proposto da Bruno e Tomassetti (2004) serve a calcolare rapidamente, sia pure in modo approssimato, la somma di variabili aleatorie discrete mutualmente indipendenti (ma non necessariamente identicamente distribuite). Tale metodo risulta molto utile specie nelle applicazioni attuariali dove le variabili aleatorie che si usano sono, nella quasi totalità dei casi, discrete. Nello specifico si compara, in questo lavoro, con altri metodi (esatti o approssimati) che esistono in letteratura per calcolare le convoluzioni. I metodi con cui si fa il confronto sono il Metodo ricorsivo di Dhane e Vandebroek (1995) e di De Pril (1985) e il metodo FFT (Fast Fourier Transform). Nel lavoro il confronto viene effettuato in termini di numero di moltiplicazioni e di tempi di elaborazioni. In entrambi i casi il metodo FDC risulta di gran lunga migliore secondo i parametri usati nel confronto e si nota come l’approssimazione del metodo risulta essere pressoché ininfluente ai fini del calcolo. Il lavoro si conclude con un esempio di calcolo con FDC in un modello individuale con 8 variabili aleatorie non identicamente distribuite per un totale di 13.500 convoluzioni.
Chemokine CXCL10 Promotes Atherogenesis by Modulating the Local Balance of Effector and Regulatory T Cells (2006)

We provide novel evidence for a functional role for the effector T-cell chemoattractant CXCL10 in atherosclerotic lesion formation by modulating the local balance of the effector and regulatory arms of the immune system.
Enzymatic Labeling of Proteins: Techniques and Approaches (2013)

Site-specific modification of proteins is a major challenge in modern chemical biology due to the large number of reactive functional groups typically present in polypeptides. Because of its importance in biology and medicine, the development of methods for site-specific modification of proteins is an area of intense research. Selective protein modification procedures have been useful for oriented protein immobilization, for studies of naturally occurring post-translational modifications, for creating antibody–drug conjugates, for the introduction of fluorophores and other small molecules on to proteins, for examining protein structure, folding, dynamics, and protein–protein interactions, and for the preparation of protein–polymer conjugates. One of the most important approaches for protein labeling is to incorporate bioorthogonal functionalities into proteins at specific sites via enzymatic reactions. The incorporated tags then enable reactions that are chemoselective, whose functional groups not only are inert in biological media, but also do not occur natively in proteins or other macromolecules. This review article summarizes the enzymatic strategies, which enable site-specific functionalization of proteins with a variety of different functional groups. The enzymes covered in this review include formylglycine generating enzyme, sialyltransferases, phosphopantetheinyltransferases, O-GlcNAc post-translational modification, sortagging, transglutaminase, farnesyltransferase, biotin ligase, lipoic acid ligase, and N-myristoyltransferase.
Current Management of Castrate-Resistant Prostate Cancer (2010)

Prostate cancer (PCa) is the most frequently diagnosed cancer in North America. Castrate-resistant PCa presents a spectrum of disease ranging from rising PSA levels in the absence of metastases or symptoms and despite androgen-deprivation therapy, to metastases and significant debilitation from cancer symptoms. Castrate-resistant PCa is usually suspected in patients with new symptoms on androgen deprivation therapy, with a rising PSA, or with new evidence of disease on bone scans or computed tomography scans. Institution of treatment and the choice of systemic or local therapy depend on a number of factors. This review discusses the various currently available treatments for patients with castrate-resistant PCa, from secondary hormonal manipulations to options for post-docetaxel systemic therapy.
[The treatment of chronic adhesive otitis by tympanoplasty and active self-insufflation according to valsalva (author's transl)]. (1981)

More than one year after tympanoplasty 85 to 95% of the followed up middle ears are aerated. The percentage depends on the degree of the preoperative adhesive process. We see the reason of this surprising success on the one hand in some special steps during operation (consequent silastic sheeting, preservation of the posterior bony canal with a deep middle ear cleft, visualisation of the tympanic orifice of the tube, widening of the natural connection between tympanon and mastoid without opening the chorda-facial-angle, some times mastoidectomy), on the other hand in a consequent postoperative follow up together with the surgeon until the ear is surely aerated controlled by self-insufflation (Valsalva). Therefore a preoperative tubal dysfunction is no contraindication for tympanoplasty: all ears should be operated. Because of the good results in hearing after just one operation, we try to rebuild the ossicular chain during the first intervention to avoid as often as possible a staged surgery.
Production of neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in carcinoma patients following GM-CSF combination therapy (1996)

In this study, the development of neutralizing and non-neutralizing GM-CSF antibodies and the clinical consequences related to the induction of these antibodies were analysed in 20 patients with metastatic colorectal carcinoma receiving a combination therapy of Escherichia coli-derived GM-CSF and a colon carcinoma-reactive MoAb in the absence of any concomitant chemotherapy. The recombinant human GM-CSF was administered subcutaneously for 10 days every month for 4 months. Following the first cycle of treatment, no GM-CSF antibodies were detected, but during subsequent therapy, 19 of the 20 patients studied developed GM-CSF binding antibodies. However, only a proportion (40%) of the 19 antibody-positive patients developed antibodies that neutralized the biological activity of GM-CSF in an in vitro bioassay. The presence of GM-CSF neutralizing antibodies was associated with a significant reduction in GM-CSF-induced expansion of leucocytes, neutrophils and eosinophils. Such clinical effects were not apparent in patients with non-neutralizing antibodies. Further characterization of sera from patients with neutralizing antibodies showed that, in most cases, the antibodies neutralized the biological activity of GM-CSF preparations derived using different expression systems (Chinese hamster ovary cells and yeast), suggesting that these antibodies may have the potential to cross-react with endogenously produced GM-CSF. These effects should be considered before therapeutic use of cytokines, particularly in patients who are not immunosuppressed, and therefore capable of mounting an effective immune response. Our results indicate that assessment of production of neutralizing antibodies induced during cytokine therapy can be used to predict diminished clinical response to further therapy.
Curves-on-Surface: A General Shape Comparison Framework. (2006)

We develop a new surface matching framework to handle surface comparisons based on the mathematical analysis of curves on surfaces, and propose a unique signature for any closed curve on a surface. The signature describes not only the shape of the curve, but also the intrinsic relationship between the curve and its embedding surface; and furthermore, the signature metric is stable across surfaces sharing similar Riemannian geometry metrics. Based on this theoretical advance, we analyze and align features defined as closed curves on surfaces using their signatures. These curves segment a surface into different regions which are mapped onto canonical domains for the matching purpose. The experimental results are very promising, demonstrating that the curve signatures and the comparison framework are robust and discriminative for the effective shape comparison. Besides its utility in our current framework, we believe the curve signature will also serve as a powerful shape segmentation/mapping tool and can be used to aid in many existing techniques towards effective shape analysis. © 2006 IEEE.
Tracking the Evolution of Non–Small-Cell Lung Cancer (2017)

Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).
Pyrrolopyrimidine nucleosides. 18, Synthesis and chemotherapeutic activity of 4-amino-7-(3-deoxy-.beta.-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide (3'-deoxysangivamycin) and 4-amino-7-(2-deoxy-.beta.-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide (2'-deoxysangivamycin) (1983)

A multistep synthesis, using the nucleoside antibiotic toyocamycin as the starting material, has furnished 6,2'-S-cyclosangivamycin (6). Desulfurization of 6,2'-S-cyclosangivamycin (6) with Raney nickel has provided 2'-deoxysangivamycin (7). Treatment of sangivamycin (1c) with sodium iodide and alpha-acetoxyisobutyryl chloride has furnished 4-amino-7-[2-O-acetyl-3-deoxy-3-iodo-5-O-(2,5,5-trimethyl-4-oxo-1, 3-dioxolan-2-yl)-beta-D-xylofuranosyl]-pyrrolo[2,3-d] pyrimidine-5-carboxamide (8a). Dehalogenation of 8a with 10% palladium on charcoal was followed by a removal of the blocking groups with ammonium hydroxide to give 3'-deoxysangivamycin (9) in 49% overall yield. The reaction of sangivamycin (1c) with diphenyl disulfide and tributylphosphine gave 5'-(phenylthio)-5'-deoxysangivamycin (10). Treatment of 10 with Raney Nickel afforded 5'-deoxysangivamycin (11). Antitumor evaluation showed that 3'-deoxysangivamycin had significant activity against the murine leukemia L1210 both in vivo and in vitro, although it was less potent on a molar basis than the parent compound sangivamycin. The 2'- and 5'-deoxysangivamycins did not show significant antitumor activity.