gebhart/patrepeval huggingface dataset:
Crosstalk between Mast Cells and Pancreatic Cancer Cells Contributes to Pancreatic Tumor Progression (2010)

Tumor-infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promotes tumor growth and invasion.
Adsorption of Viruses by Diatomaceous Earth Coated with Metallic Oxides and Metallic Peroxides (1991)

Diatomaceous earth coated with oxides of aluminium, calcium, iron, magnesium, or manganese were not found to be useful for recovering viruses from water. The oxide coatings were not stable in water or only adsorbed viruses in small volumes of water. Further modification of coatings of magnesium oxide to make magnesium peroxide produced a modified diatomaceous earth that efficiently adsorbed viruses in water. Filters containing 3.5 g of diatomaceous earth adsorbed an average of greater than 90% of MS2, polio 1, coxsackie B5, and echo 5 in tapwater at approximately pH 8.5, even after 100 liters of tapwater had passed through the filters. From 15 to 40% of MS2 or enteroviruses could be recovered from tapwater using filters containing diatomaceous earth coated with magnesium peroxide.
Dynamics of the Interaction of Human IgG Subtype Immune Complexes with Cells Expressing R and H Allelic Forms of a Low-Affinity Fcγ Receptor CD32A (2009)

CD32A, the major phagocytic FcgammaR in humans, exhibits a polymorphism in the ligand binding domain. Individuals homozygous for the R allelic form of CD32A (CD32A(R) allele) are more susceptible to bacterial infections and autoimmune diseases as compared with H allelic CD32A (CD32A(H)) homozygous and CD32A(R/H) heterozygous individuals. To understand the mechanisms behind this differential susceptibility, we have investigated the dynamics of the interaction of these allelic forms of CD32A when they are simultaneously exposed to immune complexes (IC). Binding studies using Ig fusion proteins of CD32A alleles showed that the R allele has significantly lower binding not only to human IgG2, but also to IgG1 and IgG3 subtypes. Competition assays using purified molecules demonstrated that CD32A(H)-Ig outcompetes CD32A(R)-Ig for IC binding when both alleles simultaneously compete for the same ligand. CD32A(H)-Ig blocked the IC binding mediated by both the allelic forms of cell surface CD32A, whereas CD32A(R)-Ig blocked only CD32A(R) and was unable to cross-block IC binding mediated by CD32A(H). Two-dimensional affinity measurements also demonstrated that CD32A(R) has significantly lower affinity toward all three subtypes as compared with CD32A(H). Our data suggest that the lower binding of CD32A(R) not only to IgG2 but also to IgG1 and IgG3 might be responsible for the lack of clearance of IC leading to increased susceptibility to bacterial infections and autoimmune diseases. Our data further suggests that in humans, inflammatory cells from CD32A(R/H) heterozygous individuals may predominantly use the H allele to mediate Ab-coated target cell binding during phagocytosis and Ab-dependent cellular cytotoxicity, resulting in a phenotype similar to CD32A(H) homozygous individuals.
High Tolerance and Delayed Elastic Response of Cultured Axons to Dynamic Stretch Injury (1999)

Although axonal injury is a common feature of brain trauma, little is known of the immediate morphological responses of individual axons to mechanical injury. Here, we developed an in vitro model system that selectively stretches axons bridging two populations of human neurons derived from the cell line N-Tera2. We found that these axons demonstrated a remarkably high tolerance to dynamic stretch injury, with no primary axotomy at strains <65%. In addition, the axolemma remained impermeable to small molecules after injury unless axotomy had occurred. We also found that injured axons exhibited the behavior of "delayed elasticity" after injury, going from a straight orientation before injury to developing an undulating course as an immediate response to injury, yet gradually recovering their original orientation. Surprisingly, some portions of the axons were found to be up to 60% longer immediately after injury. Subsequent to returning to their original length, injured axons developed swellings of appearance remarkably similar to that found in brain-injured humans. These findings may offer insight into mechanical-loading conditions leading to traumatic axonal injury and into potential mechanisms of axon reassembly after brain trauma.
Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXR alpha and retinoic acid. (1992)

The gene coding for apolipoprotein AI (apoAI), a lipid binding protein involved in the transport of cholesterol and other lipids in the plasma, is expressed in mammals predominantly in the liver and the intestine. Liver-specific expression is controlled by synergistic interactions between transcription factors bound to three separate sites, sites A (-214 to -192), B (-169 to -146), and C (-134 to -119), within a powerful liver-specific enhancer located between nucleotides -222 and -110 upstream of the apoAI gene transcription start site (+1). Previous studies in our laboratory have shown that ARP-1, a member of the nuclear receptor superfamily whose ligand is unknown (orphan receptor), binds to site A and represses transcription of the apoAI gene in liver cells. In a more recent series of experiments, we found that site A is a retinoic acid (RA) response element that responds preferentially to the recently identified RA-responsive receptor RXR alpha over the previously characterized RA receptors RAR alpha and RAR beta. In this study we investigated the combined effects of ARP-1 and RXR alpha on apoAI gene expression in liver cells. Transient transfection assays showed that site A is necessary and sufficient for RXR alpha-mediated transactivation of the apoAI gene basal promoter in human hepatoma HepG2 cells in the presence of RA and that this transactivation is abolished by increasing amounts of cotransfected ARP-1. Electrophoretic mobility shift assays and subsequent Scatchard analysis of the data revealed that ARP-1 and RXR alpha bind to site A with similar affinities. These assays also revealed that ARP-1 and RXR alpha bind to site A as heterodimers with an affinity approximately 10 times greater than that of either ARP-1 or RXR alpha alone. Further transfection assays in HepG2 cells, using as a reporter a construct containing the apoAI gene basal promoter and its upstream regulatory elements (including site A) in their natural context, revealed that RXR alpha has very little effect on the levels of expression regardless of the presence or absence of RA. However, while ARP-1 alone or ARP-1 and RXR alpha together dramatically repress expression in the absence of RA, the repression by ARP-1 and RXR alpha together, but not ARP-1 alone, is almost completely alleviated in the presence of RA. These results indicate that transcriptional repression by ARP-1 sensitizes apoAI gene responsiveness to RXR alpha and RA and suggest that the magnitude of this responsiveness is regulated by the intracellular ratio of ARP-1 to RXR alpha. These observations raise the possibility that transcriptional repression is a general mechanism for switching gene transcription between alternative transcription activation pathways.
Comparison of conjugates composed of lipopolysaccharide from Shigella flexneri type 2a detoxified by two methods and bound to tetanus toxoid (1994)

Shigella flexneri type 2a lipopolysaccharide (LPS) was detoxified with acetic acid (O-SP) or with hydrazine (DeALPS). DeALPS, but not O-SP, retained part of its lipid A. Both gave an identical line of precipitation with typing antiserum by double immunodiffusion, and both had low levels of LPS activity by the Limulus amoebocyte lysate assay. O-SP had an M(r) of approximately 17,000. DeALPS had two components of M(r)s approximately 30,00 (major and approximately 10,000 (minor). Adipic acid hydrazide derivatives of O-SP and DeALPS were conjugated to tetanus toxoid (TT), purified by gel filtration through CL-6B Sepharose, and designated O-SP-TT and DeALPS-TT, respectively. Saccharide (2.5 micrograms) as O-SP, DeALPS, or their conjugates was injected subcutaneously into 5-week-old mice three times 2 weeks apart. The mice were bled before the second injection and 7 days after the second and third. O-SP alone did not elicit immunoglobulin M (IgM) or IgG LPS antibodies. DeALPS elicited low levels of IgM LPS antibodies after the third injection only. Two of three lots of O-SP-TT induced significant levels of IgM LPS antibodies after the third injection. One O-SP-TT lot elicited IgG LPS antibodies after the second injection, and all three lots elicited significant levels of IgG after the third. DeALPS-TT induced low levels of anti-LPS IgM and IgG only after the third injection. The geometric mean antibody titers of both immunoglobulin classes induced by O-SP-TT were higher than those induced by DeALPS-TT. By these criteria, O-SP provided a more immunogenic saccharide than DeALPS for S. flexneri type 2a conjugates.
High-brightness fiber-coupled pump laser development (2010)

We report on the continued development of high brightness laser diode modules at nLIGHT Photonics. These modules, based on nLIGHT's Pearl<sup>TM</sup> product platform, demonstrate excellence in output power, brightness, wavelength stabilization, and long wavelength performance. This system, based on 14 single emitters, is designed to couple diode laser light into a 105 &mu;m fiber at an excitation NA of under 0.14. We demonstrate over 100W of optical power at 9xx nm with a diode brightness exceeding 20 MW/cm2-str with an operating efficiency of approximately 50%. Additional results show over 70W of optical coupled at 8xx nm. Record brilliance at wavelengths 14xx nm and longer will also be demonstrated, with over 15 W of optical power with a beam quality of 7.5 mm-mrad. These results of high brightness, high efficiency, and wavelength stabilization demonstrate the pump technology required for next generation solid state and fiber lasers.
Adenovirus Binding to Blood Factors Results in Liver Cell Infection and Hepatotoxicity (2005)

Adenoviruses (Ad) are efficient vehicles for gene delivery in vitro and in vivo. Therefore, they are a promising tool in gene therapy, particularly in the treatment of cancer and cardiovascular diseases. However, preclinical and clinical studies undertaken during the last decade have revealed a series of problems that limit both the safety and efficacy of Ad vectors, specifically after intravenous application. Major obstacles to clinical use include innate toxicity and Ad sequestration by nontarget tissues. The factors and mechanisms underlying these processes are poorly understood. The majority of intravenously injected Ad particles are sequestered by the liver, which in turn causes an inflammatory response characterized by acute transaminitis and vascular damage. Here, we describe a novel pathway that is used by Ad for infection of hepatocytes and Kupffer cells upon intravenous virus application in mice. We found that blood factors play a major role in targeting Ad vectors to hepatic cells. We demonstrated that coagulation factor IX and complement component C4-binding protein can bind the Ad fiber knob domain and provide a bridge for virus uptake through cell surface heparan sulfate proteoglycans and low-density lipoprotein receptor-related protein. An Ad vector, Ad5mut, which contained mutations in the fiber knob domain ablating blood factor binding, demonstrated significantly reduced infection of liver cells and liver toxicity in vivo. This study contributes to a better understanding of adenovirus-host interactions for intravenously applied vectors. It also provides a rationale for novel strategies to target adenovirus vector to specific tissues and to reduce virus-associated toxicity after systemic application.
Functional selection and systematic analysis of intronic splicing elements identify active sequence motifs and associated splicing factors (2010)

Despite the critical role of pre-mRNA splicing in generating proteomic diversity and regulating gene expression, the sequence composition and function of intronic splicing regulatory elements (ISREs) have not been well elucidated. Here, we employed a high-throughput in vivo Screening PLatform for Intronic Control Elements (SPLICE) to identify 125 unique ISRE sequences from a random nucleotide library in human cells. Bioinformatic analyses reveal consensus motifs that resemble splicing regulatory elements and binding sites for characterized splicing factors and that are enriched in the introns of naturally occurring spliced genes, supporting their biological relevance. In vivo characterization, including an RNAi silencing study, demonstrate that ISRE sequences can exhibit combinatorial regulatory activity and that multiple trans-acting factors are involved in the regulatory effect of a single ISRE. Our work provides an initial examination into the sequence characteristics and function of ISREs, providing an important contribution to the splicing code.
Improved Marker Combination for Detection of De Novo Genetic Variation and Aberrant DNA in Colorectal Neoplasia (2006)

We demonstrate improved sensitivity of a new marker formulation (V2) to detect aberrant DNA in CRC and precancerous adenoma tumor tissues.
Gravity inversion using seminorm minimization; density modeling of Jasper Seamount (1991)

Abstract A gravity inversion algorithm for modeling discrete bodies with nonuniform density distributions is presented. The algorithm selects the maximally uniform model from the family of models which fit the data, ensuring a conservative and unprejudiced estimate of the density variation within the body. The only inputs required by the inversion are the gravity anomaly field and the body shape. Tests using gravity anomalies generated from synthetic bodies confirm that seminorm minimizing inversions successfully represent mass distribution trends but do not reconstruct sharp discontinuities. We apply the algorithm to model the density structure of seamounts. Inversion of the sea-surface gravity field observed over Jasper Seamount suggests the edifice has a low average density of 2.38 g/cm 3 and contains a dense body within its western flank. These results are consistent with seismic, magnetic, and petrologic studies of Jasper Seamount.
Expression of cyclin-dependent kinase inhibitor p21 in human liver (1998)

The p21 protein is a universal inhibitor of cyclin-dependent kinases and of cell-cycle progression and is involved in numerous growth-inhibitory pathways in cell culture systems. Recent studies suggest that p21 regulates hepatocyte cell cycle progression in models of liver regeneration. The present study was designed to investigate the possible involvement of p21 in the control of hepatocyte proliferation in human liver diseases. To examine that, the expression of p21 in clinical liver biopsy specimens was determined by immunohistochemistry. This was correlated with hepatocyte Ki-67 immunostaining (a marker of hepatocyte proliferation in vivo) as well as histologic features. Little p21 or Ki-67 expression was detected in normal human liver or in specimens of nonalcoholic steatohepatitis. In patients with alcoholic hepatitis, increased expression of p21, but not of Ki-67, was observed. In specimens with chronic hepatitis C, hepatocyte p21 expression was significantly correlated with Ki-67 immunostaining, as well as with the degree of inflammation and fibrosis. These results indicate that hepatocyte p21 expression is upregulated in response to hepatic injury and correlates with histologic markers of proliferation and disease activity. This study provides evidence that p21 plays a role in the regulation of hepatocyte proliferation in human liver diseases.
Parameter Estimation in Biochemical Pathways: A Comparison of Global Optimization Methods (2003)

Here we address the problem of parameter estimation (inverse problem) of nonlinear dynamic biochemical pathways. This problem is stated as a nonlinear programming (NLP) problem subject to nonlinear differential-algebraic constraints. These problems are known to be frequently ill-conditioned and multimodal. Thus, traditional (gradient-based) local optimization methods fail to arrive at satisfactory solutions. To surmount this limitation, the use of several state-of-the-art deterministic and stochastic global optimization methods is explored. A case study considering the estimation of 36 parameters of a nonlinear biochemical dynamic model is taken as a benchmark. Only a certain type of stochastic algorithm, evolution strategies (ES), is able to solve this problem successfully. Although these stochastic methods cannot guarantee global optimality with certainty, their robustness, plus the fact that in inverse problems they have a known lower bound for the cost function, make them the best available candidates.
Ruthenium half-sandwich complexes as protein kinase inhibitors: derivatization of the pyridocarbazole pharmacophore ligand (2007)

A general route to ruthenium pyridocarbazole half-sandwich complexes is presented and applied to the synthesis of sixteen new compounds, many of which have modulated protein kinase inhibition properties. For example, the incorporation of a fluorine into the pyridine moiety increases the binding affinity for glycogen synthase kinase 3 by almost one order of magnitude. These data are supplemented with cyclic voltammetry experiments and a protein co-crystallographic study.
Perspectives in biochemistry (1989)

This second volume of concise and authoritative articles reports on the exciting advances and progress in the diversified areas of biochemical research. First published in ACS's renowned journal Biochemistry in 1989 and 1990, these 29 articles were written by experts in the field. They inform the general reader of the past developments, the current status, and the future direction of areas of particular significance, including: structure and function of proteins; enzyme structure and mechanism; membrane proteins and transmembrane phenomena; nucleic acids and protein biosynthesis; proteolytic processing and protein degradation; cell growth and regulation; and bioenergetics.
Recruitment of RNA polymerase III to its target promoters (2002)

A key step in retrieving the information stored in the complex genomes of eukaryotes involves the identification of transcription units and, more specifically, the recognition of promoter sequences by RNA polymerase. In eukaryotes, the task of recognizing nuclear gene promoters and then transcribing the genes is divided among three highly related enzymes, RNA polymerases I, II, and III. Each of these RNA polymerases is dedicated to the transcription of specific sets of genes, and each depends on accessory factors, the so-called transcription factors, to recognize its cognate promoter sequences.
Atoms, molecules, solids, and surfaces: Applications of the generalized gradient approximation for exchange and correlation (1992)

Generalized gradient approximations (GGA's) seek to improve upon the accuracy of the local-spin-density (LSD) approximation in electronic-structure calculations. Perdew and Wang have developed a GGA based on real-space cutoff of the spurious long-range components of the second-order gradient expansion for the exchange-correlation hole. We have found that this density functional performs well in numerical tests for a variety of systems: (1) Total energies of 30 atoms are highly accurate. (2) Ionization energies and electron affinities are improved in a statistical sense, although significant interconfigurational and interterm errors remain. (3) Accurate atomization energies are found for seven hydrocarbon molecules, with a rms error per bond of 0.1 eV, compared with 0.7 eV for the LSD approximation and 2.4 eV for the Hartree-Fock approximation. (4) For atoms and molecules, there is a cancellation of error between density functionals for exchange and correlation, which is most striking whenever the Hartree-Fock result is furthest from experiment. (5) The surprising LSD underestimation of the lattice constants of Li and Na by 3--4 % is corrected, and the magnetic ground state of solid Fe is restored. (6) The work function, surface energy (neglecting the long-range contribution), and curvature energy of a metallic surface are all slightly reduced in comparison with LSD. Taking account of the positive long-range contribution, we find surface and curvature energies in good agreement with experimental or exact values. Finally, a way is found to visualize and understand the nonlocality of exchange and correlation, its origins, and its physical effects.
Overexpression of sialyltransferase CMP-sialic acid:Galbeta1,3GalNAc-R alpha6-Sialyltransferase is related to poor patient survival in human colorectal carcinomas. (2001)

Thomsen-Friedenreich (TF)-related blood group antigens, such as TF, Tn, and their sialylated variants, belong to a family of tumor-associated carbohydrates. The aim of the present study was to examine tumor-associated alterations of glycosyltransferases involved in the biosynthesis of the TF glycotope in colorectal carcinomas. To this end, glycosyltransferase expression was examined in 40 cases of colorectal carcinoma specimens classified according to the WHO/Union International Contre Cancer guidelines and in "normal" mucosa of the same patients. Occurrence of TF glycotope was examined by immunohistochemistry with the monoclonal antibody A78-G/A7. Expression of sialyltransferases CMP-sialic acid:Galbeta1,3GalNAc-R alpha3-sialyltransferase I and II (ST3Gal-I and ST3Gal-II) and CMP-sialic acid:Galbeta1,3GalNAc-R alpha6-sialyltransferase (ST6GalNAc-II) and of core 2 beta1,6-N-acetylglucosaminyltransferase was determined by reverse transcription-PCR in the same cryostat sections used for immunohistochemistry. Additionally, alpha2,3-sialyltransferase enzyme activity was studied in each of these tissues. The TF glycotope was detected in 7% of the normal mucosa, but in 57% of the carcinoma samples. Expression of alpha2,3-sialyltransferases ST3Gal-I, ST3Gal-II, and enzyme activity of alpha2,3-sialyltransferase was significantly increased (P < 0.001) in carcinoma specimens compared with normal mucosa. ST3Gal-I mRNA expression was significantly increased (P = 0.05) in cases showing invasion of lymph vessels. Expression of ST6GalNAc-II was significantly increased (P = 0.04) in cases with metastases to lymph nodes along the vascular trunk. Moreover, ST6GalNAc-II expression provides an prognostic factor for patient survival (log rank, P = 0.02). In an attempt to study the functional relevance of the glycosyltransferases for TF biosynthesis, SW480 colorectal cells were transfected with each of the enzymes, and cell surface expression of the TF glycotope was examined by flow cytometry. The presence of TF was not altered by transfection of the cells with either sialyltransferase ST3Gal-I or ST3Gal-II. However, successful transfection with core 2 beta1,6-N-acetylglucosaminyltransferase led to reduced expression of TF. In contrast, increased cell surface expression of TF was found after ST6GalNAc-II transfection. Thus, expression of TF on the cell surface of SW480 colorectal carcinoma cells depends on the ratio of core 2 beta1,6-N-acetylglucosaminyltransferase and ST6GalNAc-II. Earlier immunohistological studies demonstrated that TF is a prognostic factor for patient survival. Our results suggest that sialyltransferase ST6GalNAc-II is of crucial relevance for the prognostic significance of TF.