gebhart/patrepeval huggingface dataset:
Temperature Effects on Free-Thyroxine Measurements: Analytical and Clinical Consequences (1992)

We compared the analytical and clinical performance of two free-thyroxine (FT4) assays--a solid-phase radioimmunoassay, Spectria, and a time-resolved fluoroimmunoassay, Delfia, both of them two-step methods--with the performance of a direct radioimmunoassay, Nichols, to measure FT4 concentration in equilibrium dialysate of undiluted serum. The three assays showed comparable analytical performance. We tested clinical utility in sera from 135 healthy subjects with and without thyroxine-binding abnormalities and in 61 patients with and without thyroidal illnesses. We found significant differences for FT4 measured by different assays in sera from the same euthyroid patients. To explain the differences, we studied the influence of temperature on performance and calibration. Most important was the neglected fact that the association constant for the binding of thyroxine to thyroxine-binding globulin decreases when the temperature rises from 20 to 37 degrees C, causing a doubling of FT4. The two-step assays, if performed at room temperature without a well-defined calibration, can give misleading FT4 concentrations. This is the case when sera from patients with thyroxine-binding abnormalities are measured against kit standards, made up in normal human sera. If an assay is to reflect the in vivo FT4 concentration at body temperature in all types of samples, it should be performed at body temperature. For practical reasons 37 degrees C is recommended, and reference values should be defined at 37 degrees C. The same might be valid for other free-hormone assays.
A Defined Subset of Adenylyl Cyclases Is Regulated by Bicarbonate Ion (2003)

The molecular basis by which organisms detect and respond to fluctuations in inorganic carbon is not known. The cyaB1 gene of the cyanobacterium Anabaena sp. PCC7120 codes for a multidomain protein with a C-terminal class III adenylyl cyclase catalyst that was specifically stimulated by bicarbonate ion (EC50 9.6 mm). Bicarbonate lowered substrate affinity but increased reaction velocity. A point mutation in the active site (Lys-646) reduced activity by 95% and was refractory to bicarbonate activation. We propose that Lys-646 specifically coordinates bicarbonate in the active site in conjunction with an aspartate to threonine polymorphism (Thr-721) conserved in class III adenylyl cyclases from diverse eukaryotes and prokaryotes. Using recombinant proteins we demonstrated that adenylyl cyclases that contain the active site threonine (cyaB of Stigmatella aurantiaca and Rv1319c of Mycobacterium tuberculosis) are bicarbonate-responsive, whereas adenylyl cyclases with a corresponding aspartate (Rv1264 of Mycobacterium) are bicarbonate-insensitive. Large numbers of class III adenylyl cyclases may therefore be activated by bicarbonate. This represents a novel mechanism by which diverse organisms can detect bicarbonate ion.
Suppressors of a gpa1 mutation cause sterility in Saccharomyces cerevisiae. (1988)

The Saccharomyces cerevisiae GPA1 gene encodes a protein highly homologous to the alpha subunit of mammalian G proteins and is essential for haploid cell growth. We have selected 77 mutants able to suppress the lethality resulting from disruption of GPA1 (gpa1::HIS3). Two strains bearing either of two recessive mutations, sgp1 and sgp2, in combination with the disruption mutation, showed a cell type nonspecific sterile phenotype, yet expressed the major alpha-factor gene (MF alpha 1) as judged by the ability to express a MF alpha 1-lacZ fusion gene. The sgp1 mutation was closely linked to gpa1::HIS3 and probably occurred at the GPA1 locus. The sgp2 mutation was not linked to GPA1 and was different from the previously identified cell type nonspecific sterile mutations (ste4, ste5, ste7, ste11 and ste12). sgp2 GPA1 cells showed a fertile phenotype, indicating that the mating defect caused by sgp2 is associated with the loss of GPA1 function. While expression of a FUS1-lacZ fusion gene was induced in wild-type cells by the addition of alpha-factor, mutants bearing sgp1 or sgp2 as well as gpa1::HIS3 constitutively expressed FUS1-lacZ. These observations suggest that GPA1 (SGP1) and SGP2 are involved in mating factor-mediated signal transduction, which causes both cell cycle arrest in the late G1 phase and induction of genes necessary for mating such as FUS1.
The Junction Between the Left Atrium and the Pulmonary Veins (1966)

Some anatomic features of the posterior wall of the left atrium, the atrial-pulmonary venous junctions, and the myocardial sleeves extending over the pulmonary veins, as observed in 16 human hearts, are described. Different patterns of direction of the myocardial fibers of the atrial wall were found in the different specimens. The atrial wall between the upper pulmonary veins was consistently thicker than that between the lower ones. Similarly, the sphincter-like structures of the atrial-pulmonary venous junctions were generally more conspicuous, and the myocardial venous sleeves better developed in the superior than in the inferior pulmonary veins. The physiological and pathological implications of these findings are discussed.
Ethylene Insensitivity Conferred by Arabidopsis ERS Gene (1995)

ERS (ethylene response sensor), a gene in the Arabidopsis thaliana ethylene hormone-response pathway, was uncovered by cross-hybridization with the Arabidopsis ETR1 gene. The deduced ERS protein has sequence similarity with the amino-terminal domain and putative histidine protein kinase domain of ETR1, but it does not have a receiver domain as found in ETR1. A missense mutation identical to the dominant etr1-4 mutation was introduced into the ERS gene. The altered ERS gene conferred dominant ethylene insensitivity to wild-type Arabidopsis. Double-mutant analysis indicates that ERS acts upstream of the CTR1 protein kinase gene in the ethylene-response pathway.
An analysis of the relationship between metastases and cachexia in lung cancer patients (2016)

Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co-occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P < 0.0001] treatment, respectively). The change in number of metastatic sites over time correlated with increasing weight loss (5.2%, 10.6%, 13.4%, and 13.4%, for an increase of 0, 1, 2, and ≥3 metastatic sites, from initial diagnosis to the endpoint; P < 0.0001). Patients with cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08-4.16; P < 0.0001). Tumors with mutated KRAS were associated with an increased risk of weight loss (11.4% weight loss in patients with mutated KRAS vs. 6.0% in patients with wild-type KRAS; P = 0.0011). Our findings suggest that the capabilities of lung cancer to metastasize and cause cachexia might be linked intrinsically and are independent of treatments administered. KRAS-mutated tumors were more commonly associated with cachexia.
A general cone-beam reconstruction algorithm (1993)

Considering the characteristics of the X-ray microscope system being developed at SUNY at Buffalo and the limitations of available cone-beam reconstruction algorithms, a general cone-beam reconstruction algorithm and several special versions of it are proposed and validated by simulation. The cone-beam algorithm allows various scanning loci, handles reconstruction of rod-shaped specimens which are common in practice, and facilitates near real-time reconstruction by providing the same computational efficiency and parallelism as L.A. Feldkamp et al.'s (1984) algorithm. Although the present cone-beam algorithm is not exact, it consistently gives satisfactory reconstructed images. Furthermore, it has several nice properties if the scanning locus meets some conditions. First, reconstruction within a midplane is exact using a planar scanning locus. Second, the vertical integral of a reconstructed image is equal to that of the actual image. Third, reconstruction is exact if an actual image is independent of rotation axis coordinate z. Also, the general algorithm can uniformize and reduce z-axis artifacts, if a helix-like scanning locus is used.
Bax Can Antagonize Bcl-XL during Etoposide and Cisplatin-induced Cell Death Independently of Its Heterodimerization with Bcl-XL (1996)

Bax, a member of the Bcl-2 family of proteins, has been shown to promote apoptosis while other members of the family, including Bcl-XL and Bcl-2, inhibit cell death induced by a variety of stimuli. The mechanism by which Bax promotes cell death is poorly understood. In the present report, we assessed the ability of Bax to antagonize the death repressor activity of Bcl-XL during chemotherapy-induced apoptosis in the lymphoid cell line, FL5.12. Expression of wild-type Bax countered the repressor activity of Bcl-XL against cell death mediated by VP-16 and cisplatin. We performed site-directed mutagenesis of the BH1, BH2, and BH3 homology regions in Bax to determine the ability of wild-type and mutant Bax to heterodimerize with Bcl-XL and to antagonize the protective effect of Bcl-XL against chemotherapy-induced apoptosis. Bax proteins expressing alanine substitutions of the highly conserved amino acids glycine 108 in BH1, tryptophan 151 and 158 in BH2, and glycine 67 and aspartic acid 68 in BH3 retained their ability to promote chemotherapy-induced cell death that was inhibited by Bcl-XL and to form heterodimers with Bcl-XL. Bax proteins containing deletions of the most highly conserved amino acids in BH1 (Delta102-112) and BH2 (Delta151-159) maintained the ability of Bax to antagonize the death repressor activity of Bcl-XL and to associate with Bcl-XL. However, Bax with BH3 deleted did not form heterodimers with Bcl-XL, but retained its ability to counter the death repressor activity of Bcl-XL. These results demonstrate that the conserved BH3, but not BH1 or BH2, homology region of Bax is necessary for its interaction with Bcl-XL in mammalian cells. Furthermore, our results indicate that Bax does not require BH1, BH2, BH3, or heterodimerization with Bcl-XL to counter the death repressor activity of Bcl-XL. Therefore, Bax can antagonize Bcl-XL during VP-16 and, in a lesser degree, during cisplatin-induced cell death independent of its heterodimerization with Bcl-XL.
A case study in application I/O on Linux clusters (2001)

A critical but often ignored component of system performance is the I/O system. Today's applications demand a great deal from underlying storage systems and software, and both high-performance distributed storage and high level interfaces have been developed to fill these needs.In this paper we discuss the I/O performance of a parallel scientific application on a Linux cluster, the FLASH astrophysics code. This application relies on three I/O software components to provide high-performance parallel I/O on Linux clusters: the Parallel Virtual File System, the ROMIO MPI-IO implementation, and the Hierarchical Data Format library. Through instrumentation of both the application and underlying system software code we discover the location of major software bottlenecks. We work around the most inhibiting of these bottlenecks, showing substantial performance improvement. We point out similarities between the inefficiencies found here and those found in message passing systems, indicating that research in the message passing field could be leveraged to solve similar problems in high-level I/O interfaces.
Single Chain Fv Antibodies against the 25−35 Aβ Fragment Inhibit Aggregation and Toxicity of Aβ42 (2006)

Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta (Abeta) protein in the brain. Immunization studies have demonstrated that anti-Abeta antibodies reduce Abeta deposition and improve clinical symptoms seen in AD. However, conventional antibody-based therapies risk an inflammatory response that can result in meningoencephalitis and cerebral hemorrhage. Here we report on the development of human-based single chain variable domain antibody fragments (scFvs) directed against the Abeta 25-35 region as potential therapeutics for AD that do not risk an inflammatory response. The 25-35 region of Abeta represents a promising therapeutic target since it promotes aggregation and is highly toxic. Two scFvs with differing affinities for Abeta were studied, and both inhibited aggregation of Abeta42 as determined by thioflavin T binding assay and atomic force microscopy analysis and blocked Abeta-induced toxicity toward human neuroblastoma SH-SY5Y cells as determined by MTT and LDH release assays. These results provide additional evidence that scFvs against Abeta provide an attractive alternative to more conventional antibody-based therapeutics for controlling aggregation and toxicity of Abeta.
Ectopic Expression of atRSZ33 Reveals Its Function in Splicing and Causes Pleiotropic Changes in Development (2003)

Splicing provides an additional level in the regulation of gene expression and contributes to proteome diversity. Herein, we report the functional characterization of a recently described plant-specific protein, atRSZ33, which has characteristic features of a serine/arginine-rich protein and the ability to interact with other splicing factors, implying that this protein might be involved in constitutive and/or alternative splicing. Overexpression of atRSZ33 leads to alteration of splicing patterns of atSRp30 and atSRp34/SR1, indicating that atRSZ33 is indeed a splicing factor. Moreover, atRSZ33 is a regulator of its own expression, as splicing of its pre-mRNA is changed in transgenic plants. Investigations by promoter-beta-glucuronidase (GUS) fusion and in situ hybridization revealed that atRSZ33 is expressed during embryogenesis and early stages of seedling formation, as well as in flower and root development. Ectopic expression of atRSZ33 caused pleiotropic changes in plant development resulting in increased cell expansion and changed polarization of cell elongation and division. In addition, changes in activity of an auxin-responsive promoter suggest that auxin signaling is disturbed in these transgenic plants.
Effect of MMP-2 Deficiency on Atherosclerotic Lesion Formation in ApoE-Deficient Mice (2006)

MMP-2 contributes to the development of atherosclerosis in apoE(-/-) mice.
Enhancement of both reaction yield and rate of synthesis of structured triacylglycerol containing eicosapentaenoic acid under vacuum with water activity control (1999)

Production of structured triacylglycerols (sTAG) containing eicosapentaenoic acid (EPA) at the sn-1 (or 3) position using Lipozyme in a solvent-free system was studied. Optimal water activity (a(w)) for the synthesis of the sTAG was investigated. Vacuum was applied to shift reaction equilibrium toward the synthesis reaction by removing by-products. During vacuum application, the water level of the reaction system was controlled at the optimal level by addition of a suitable amount of water at a predetermined interval. Intermittent periodic addition of a suitable amount of water into the reaction mixture made the reaction rate faster than that without adding water. A molar yield of 89.7% of the targeted sTAG was obtained after 16 h reaction with a(w) control during the vacuum application as compared with the yield of 87.0% after 24 h of reaction without a(w) control during the vacuum application.
Specific amplification of Ehrlichia platys DNA from blood specimens by two-step PCR (1996)

A two-step PCR method for diagnosis of canine infectious cyclic thrombocytopenia was established. Three primers derived from the 16S and rRNA gene sequence were used to amplify genomic DNA specifically from Ehrlichia platys. Two-round amplification with DNA templates prepared from E. platys-infected blood specimens produced 742- and 385-bp fragments, but these products were not found when an Ehrlichia canis-infected blood sample and Escherichia coli were used. This method, for which the minimum detectable copy number in the blood specimen was estimated to be five ehrlichia inclusion within platelets, is more sensitive than single PCR amplification. These results demonstrate that this two-step PCR is highly sensitive and efficient for detecting the etiologic agent of canine infectious cyclic thrombocytopenia in blood. The same technique was applied to blood specimens collected from a dog inoculated with E. platys. Amplification of the target DNA fragments was observed with blood collected on the fifth day after inoculation, which indicates that this method is also feasible for early diagnosis of E. platys infection.
Nuclear Localization and Formation of β-Catenin–Lymphoid Enhancer Factor 1 Complexes Are Not Sufficient for Activation of Gene Expression (1999)

In response to activation of the Wnt signaling pathway, beta-catenin accumulates in the nucleus, where it cooperates with LEF/TCF (for lymphoid enhancer factor and T-cell factor) transcription factors to activate gene expression. The mechanisms by which beta-catenin undergoes this shift in location and participates in activation of gene transcription are unknown. We demonstrate here that beta-catenin can be imported into the nucleus independently of LEF/TCF binding, and it may also be exported from nuclei. We have introduced a small deletion within beta-catenin (Delta19) that disrupts binding to LEF-1, E-cadherin, and APC but not axin. This Delta19 beta-catenin mutant localizes to the nucleus because it may not be efficiently sequestered in the cytoplasm. The nuclear localization of Delta19 definitively demonstrates that the mechanisms by which beta-catenin localizes in the nucleus are completely independent of LEF/TCF factors. beta-Catenin and LEF-1 complexes can activate reporter gene expression in a transformed T-lymphocyte cell line (Jurkat) but not in normal T lymphocytes, even though both factors are nuclear. Thus, localization of both factors to the nucleus is not sufficient for activation of gene expression. Excess beta-catenin can squelch reporter gene activation by LEF-1-beta-catenin complexes but not activation by the transcription factor VP16. Taken together, these data suggest that a third component is necessary for gene activation and that this third component may vary with cell type.
Applications of Nanoparticles in Biology (2008)

Abstract The wide variety of core materials available, coupled with tunable surface properties, make nanoparticles an excellent platform for a broad range of biological and biomedical applications. This Review provides an introduction to nanoparticle–biomolecular interactions as well as recent applications of nanoparticles in biological sensing, delivery, and imaging of live cells and tissues. magnified image
Malignant transformation by H‐ras results in aberrant regulation of ribonucleotide reductase gene expression by transforming growth factor‐β1 (1995)

Ribonucleotide reductase is a key rate-limiting and regulatory step in DNA synthesis and plays a crucial role in the coordination of DNA synthesis, DNA repair, and cell proliferation. The present study demonstrates a link between alterations in TGF-beta 1 regulation during malignant conversion and the expression of ribonucleotide reductase. H-ras-transformed mouse 10T1/2 cell lines exhibiting malignant potential were examined for possible TGF-beta 1-mediated alterations in ribonucleotide reductase expression. Selective induction of ribonucleotide reductase gene expression occurred, since only H-ras-transformed highly metastatic cells exhibited marked elevations in ribonucleotide reductase expression, whereas nontransformed normal 10T1/2 cells were unaffected by TGF-beta 1 treatment. These changes occurred without any detectable modifications in DNA synthesis rates, suggesting that these changes were regulated by a novel mechanism independent of the S-phase of the cell cycle. Furthermore, this TGF-beta 1-mediated regulation of ribonucleotide reductase expression was shown to occur through an autocrine mechanism. TGF-beta 1-modulated regulation of ribonucleotide reductase expression requires de novo protein synthesis and involves, at least in part, transcriptional and post-transcriptional events. Furthermore, evidence is presented to suggest a possible role for protein kinase C-mediated events, protein phosphatases, and G-protein-coupled events in the TGF-beta 1-mediated regulation of ribonucleotide reductase expression in H-ras-transformed malignant cells. TGF-beta 1 regulation of ribonucleotide reductase in highly malignant cells appears to be complex and multifaceted and constitutes an integral part of an altered growth regulatory program.
Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein (1989)

We have performed a detailed analysis of the biochemical properties of the human immunodeficiency virus (HIV) type 1 vpu gene product to elucidate its function during virus replication. Our data suggest that vpu is posttranslationally modified by phosphorylation, since a 16-kilodalton phosphoprotein can be specifically immunoprecipitated with both a serum from an HIV-positive individual (HIV-positive serum) and a vpu-specific antiserum. In contrast, our results suggest that vpu is not glycosylated, even though the protein contains a potential glycosylation site. In vitro translation studies demonstrated that vpu is cotranslationally integrated into microsomal membranes, suggesting that vpu is an integral membrane protein. While vpu was found in significant quantities in virus-producing cells, the protein could not be detected in cell-free culture fluids and is therefore most likely not viron associated. Processing of viral precursor proteins was unaffected by the absence of vpu, and no differences were detected in the protein compositions of wild-type and mutant virions. However, virus release from cultures producing vpu-defective virus was found to be delayed, resulting in the intracellular accumulation of viral proteins. Our data suggest that vpu has a function in the release of virus particles from infected cells.
RETRACTED ARTICLE: Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis (2015)

Our results indicated that BIO12-11 compound would be an useful tool to further understand the biological roles of VLA4/VCAM1 interactions, and could also be considered as EAE-suppressing agent.