gebhart/patrepeval huggingface dataset:
TYPE I INTERFERONS (α/β) IN IMMUNITY AND AUTOIMMUNITY (2004)

The significance of type I interferons (IFN-alpha/beta) in biology and medicine renders research on their activities continuously relevant to our understanding of normal and abnormal (auto) immune responses. This relevance is bolstered by discoveries that unambiguously establish IFN-alpha/beta, among the multitude of cytokines, as dominant in defining qualitative and quantitative characteristics of innate and adaptive immune processes. Recent advances elucidating the biology of these key cytokines include better definition of their complex signaling pathways, determination of their importance in modifying the effects of other cytokines, the role of Toll-like receptors in their induction, their major cellular producers, and their broad and diverse impact on both cellular and humoral immune responses. Consequently, the role of IFN-alpha/beta in the pathogenesis of autoimmunity remains at the forefront of scientific inquiry and has begun to illuminate the mechanisms by which these molecules promote or inhibit systemic and organ-specific autoimmune diseases.
Oxygen Saturation-Dependent Absorption and Scattering of Blood (2004)

We report on the scattering properties of oxygenated and deoxygenated whole blood from 250 to 1000 nm. We determine the complex refractive index of oxygenated and deoxygenated hemoglobin using a Kramers-Kronig analysis and optical coherence tomography measurements. Combining these data with Mie theory, the scattering properties are calculated. The strong oxygen saturation dependent scattering effects should be taken into account in the data analysis of optical oxymetry.
Alvocidib Potentiates the Activity of Azacytidine in an MCL-1-Dependent Fashion (2015)

Abstract Despite significant efforts, the clinical mechanism of action of hypomethylating agents such as 5-azacytidine (5-aza) is still poorly understood. 5-aza is currently indicated for the treatment of patients with myelodysplastic syndrome (MDS). While 5-aza has achieved good single-agent activity in acute myeloid leukemia (AML), complete response rates remain low when used as a single agent. In a recent report aimed at identifying rational therapeutic combinations with 5-aza, Bogenberger and colleagues identified multiple BCL-2 family member/BH3-containing therapeutic targets, which synergize with 5-aza when inhibited genetically or pharmacologically. The CDK9 inhibitor, alvocidib, has achieved significant improvement in complete response rates of newly diagnosed AML patients when administered before cytarabine and mitoxantrone (FLAM regimen) in a randomized multi-center Phase 2 trial when compared to 7+3 standard of care treatment. Recent reports suggest that the transcriptional repression of key anti-apoptotic proteins (eg., MCL-1) mediated by alvocidib's CDK9 inhibition, drive the pro-apoptotic activity of alvocidib in the FLAM regimen. We, therefore, hypothesized that alvocidib and 5-aza would synergize therapeutically in the treatment of AML by means of transcriptional repression of MCL-1 and sensitization to 5-aza. In this report, we demonstrate that treatment of AML cell lines with alvocidib inhibits both mRNA and protein expression of MCL-1 in a time and concentration-dependent fashion. Pre-treatment of cells with alvocidib, to repress MCL-1 expression prior to 5-aza treatment, reduced the 5-aza cell viability EC50 more than 2.5-fold, from 1.8 µM to 0.6 µM in MV4-11 cells. The alvocidib/5-aza combination also resulted in synergistic increases in caspase activity relative to either single agent within the combination, at multiple dose levels. Therefore, following reports suggesting inhibition of BCL-2 family members including MCL-1, sensitizes cells to 5-aza, our data suggest that the alvocidib/5-aza combination may constitute a viable therapeutic regimen. We also conclude that a CDK9 inhibitor/5-aza combination may be an effective clinical approach for the treatment of AML. Disclosures Kim: Tolero Pharmaceuticals: Employment. Soh:Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Lee:Tolero Pharmaceuticals: Employment. Peterson:Tolero Pharmaceuticals: Employment. Whatcott:Tolero Pharmaceuticals: Employment. Siddiqui-Jain:Tolero Pharmaceuticals: Employment. Weitman:Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Warner:Tolero Pharmaceuticals: Employment.
A Historical Comparison of Validity Standards and Validity Practices (1998)

The present study examined the relationship between the validity theory of the past 50 years with actual validity practices. This process involved the comparison of validity requirements and theory as they appeared in the published test standards (by the American Psychological Association, the American Educational Research Association, and the National Council on Measurement in Education) to the practices of measurement professionals. Each of the four sets of test standards were operationally defined and then compared to information and opinions about validity evidence expressed in the Mental Measurements Yearbook test reviews. Results from this process indicate that the theoretical modifications to the concept of validity have been carried over into validity practice. However, it was also found that operational modifications to the concept of validity have been influenced by validity practice. Therefore, there appears to be a symbiotic relationship between theory and practice on the influence of validity.
Linkage of the evolutionarily-related serum albumin and alpha-fetoprotein genes within q11-22 of human chromosome 4. (1983)

Albumin and alpha-fetoprotein are structurally related serum proteins, having a similar gene structure and, conceivably, a common evolutionary origin. To test their relative arrangement in the human genome, the serum albumin and alpha-fetoprotein genes were mapped by in situ hybridization of cloned human albumin or alpha-fetoprotein cDNA to human mitotic chromosome preparations. Analysis of cells hybridized with the serum albumin probe showed that 39% of cells exhibited grains on the proximal portion of the long arm of chromosome 4 (bands q11-22), with these grains comprising 30% of all labeled sites throughout these mitoses. Similarly, in cells hybridized with the alpha-fetoprotein probe, 39% of cells were observed to contain silver grains on 4q11-22, these grains constituting 20% of all labeled sites in these cells. These results demonstrate chromosomal localization and linkage of the serum albumin and alpha-fetoprotein genes within bands q11-22 of the long arm of human chromosome 4.
Spectral Transmission of the Human Crystalline Lens in Adult and Elderly Persons: Color and Total Transmission of Visible Light (2012)

The great variability existing in the spectral transmission of the human crystalline lens is lesser between the ages of 40 and 59 years, but greater from the age of 60 and older. The decrement in transmittance between these two age groups varies from 40% for 420 nm to 18% for 580 nm. Nevertheless, it is proven that age is not the only parameter affecting crystalline transmission. In the range of 40 to 59 years, age does not bear an influence on total transmission of light, but from 60 years and older it does. Moreover, the light transmitted decreases with age. This total transmission of light is similar to or lower than the amount that the different intraocular lenses transmit, even with a yellow or orange filter. The color of the human lens becomes yellowish and saturated with age.
Autoantigen specific T cells inhibit glutamate uptake in astrocytes by decreasing expression of astrocytic glutamate transporter GLAST: a mechanism mediated by tumor necrosis factor‐α (2005)

Glutamate excitotoxicity is increasingly being recognized as a pathogenic mechanism in autoimmune inflammatory disorders of the central nervous system (CNS). Astrocytes are the predominant players in clearing the extracellular space from glutamate and normally have extensive spare capacities in terms of glutamate uptake. We asked what might be the basis of glutamate accumulation in T cell triggered autoimmune inflammation. In vitro, coculture of primary rat astrocytes with activated myelin basic protein (MBP)-specific T cells resulted in a decrease of astrocytic glutamate uptake rates (Vmax). In parallel, the amount of the Na+-dependent glutamate transporter GLAST was reduced within 48-60 h. Significant decreases of GLAST protein were observed in astrocytes harvested after incubation with T cells activated by MBP during coculture or after incubation with T cell blasts preactivated in the presence of splenocytes beforehand. Since exposure of astrocytes to cell-free supernatant of MBP-activated T cells also resulted in reduced expression of GLAST, a humoral factor appeared to be the driving agent. In blocking experiments using neutralizing antibodies and by incubation of astrocytes with recombinant cytokines, tumor necrosis factor-alpha (TNF-alpha) was identified as being responsible for the down-modulation of GLAST. GLAST was also down-regulated in the CNS of autoimmune encephalomyelitic rats but not in animals suffering from systemic inflammation. Since the loss of GLAST was not confined to inflammatory infiltrates, here too, a humoral factor seemed to be causative. In conclusion, T cell derived TNF-alpha impairs glutamate clearance capacity of astrocytes in vitro and probably also in vivo providing a pathogenic link to glutamate excitotoxicity that may contribute to early axonal dysfunction remote from active autoimmune inflammatory demyelination.
Identification of the disulfide-linked homodimer of apolipoprotein E3 in plasma. Impact on receptor binding activity (1991)

The nature of disulfide-linked structures of apolipoprotein (apo) E3 in the plasma of E3/3 subjects was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis performed under nonreducing conditions followed by immunoblotting with apoE-specific antibodies. In addition to the expected presence of the heterodimer apoE3-A-II and monomeric apoE3, a band with an apparent Mr approximately 100,000 was also observed in plasma that had been treated with sulfhydryl-trapping reagents. This band and apoE3-A-II were both eliminated by disulfide reduction, which produced a corresponding increase in monomeric apoE3. Both bands were absent in plasma from a subject with the E4/4 phenotype. In spite of its apparent molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the high molecular weight band was demonstrated to represent the disulfide-linked homodimer of apoE3. It was isolated from purified apoE3 preparations that had undergone oxygen-mediated dimerization and shown to elute from a Sephacryl S-300 column in a position with the expected molecular weight of a homodimer. The apoE3 dimer displayed a preference for high density lipoproteins, as determined by agarose chromatography of E3/3 plasma but was stripped from high density lipoproteins by ultracentrifugation. Quantitation of the relative ratios of homodimer, apoE3-A-II, and monomer in the plasma of 22 normolipidemic E3/3 subjects by immunoblotting revealed that the disulfide-linked structures accounted for the majority (approximately 55%) of plasma apoE. Both the homodimer and apoE3-A-II displayed a reduced ability to compete with low density lipoproteins for fibroblast low density lipoprotein receptors (20 and 30% of monomeric apoE3 binding activity, respectively). These results raise the possibility that the amount or availability of receptor-active apoE3 in E3/3 subjects may be rate limiting for metabolic events involving the low density lipoprotein receptor.
New combination therapies with cell-cycle agents. (2008)

Cancer cells have deregulated cell-cycle progression with overexpression of positive regulators and inhibition of negative regulators, giving them unlimited replication potential. Therefore, development of agents targeting the deregulated cell cycle has been considered as an ideal strategy for cancer therapy. Cell-cycle-based agents have been categorized as cyclin-dependent kinase inhibitors, Cdc25 inhibitors, checkpoint inhibitors and mitotic inhibitors. These drugs have demonstrated preclinical efficacy, but their efficacy in the clinic has been modest and has been hampered by various side effects. Alternatively, their combination with chemotherapeutic drugs has been studied in different preclinical and clinical settings. Initial reports from these combination studies have been encouraging and suggest that combined drugs may be useful in lowering cancer burden.
Using Maximum Entropy for Text Classification (1999)

This paper proposes the use of maximum entropy techniques for text classification. Maximum entropy is a probability distribution estimation technique widely used for a variety of natural language tasks, such as language modeling, part-of-speech tagging, and text segmentation. The underlying principle of maximum entropy is that without external knowledge, one should prefer distributions that are uniform. Constraints on the distribution, derived from labeled training data, inform the technique where to be minimally non-uniform. The maximum entropy formulation has a unique solution which can be found by the improved iterative scaling algorithm. In this paper, maximum entropy is used for text classification by estimating the conditional distribution of the class variable given the document. In experiments on several text datasets we compare accuracy to naive Bayes and show that maximum entropy is sometimes significantly better, but also sometimes worse. Much future work remains, but the results indicate that maximum entropy is a promising technique for text classification. 1
Macromolecular Substrate Affinity for the Tissue Factor-Factor VIIa Complex Is Independent of Scissile Bond Docking (1999)

The upstream coagulation enzymes are homologous trypsin-like serine proteases that typically function in enzyme-cofactor complexes, exemplified by coagulation factor VIIa (VIIa), which is allosterically activated upon binding to its cell surface receptor tissue factor (TF). TF cooperates with VIIa to create a bimolecular recognition surface that serves as an exosite for factor X binding. This study analyzes to what extent scissile bond docking to the catalytic cleft contributes to macromolecular substrate affinity. Mutation of the P1 Arg residue in factor X to Gln prevented activation by the TF.VIIa complex but did not reduce macromolecular substrate affinity for TF.VIIa. Similarly, mutations of the S and S' subsites in the catalytic cleft of the enzyme VIIa failed to reduce affinity for factor X, although the affinity for small chromogenic substrates and the efficiency of factor X scissile bond cleavage were reduced. Thus, docking of the activation peptide bond to the catalytic cleft of this enzyme-cofactor complex does not significantly contribute to affinity for macromolecular substrate. Rather, it appears that the creation of an extended macromolecular substrate recognition surface involving enzyme and cofactor is utilized to generate substrate specificity between the highly homologous, regulatory proteases of the coagulation cascade.
Quantitative Determination of Monosaccharides as Their Alditol Acetates by Gas Liquid Chromatography. (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuantitative Determination of Monosaccharides as Their Alditol Acetates by Gas Liquid Chromatography.J. S. Sawardeker, J. H. Sloneker, and Allene. JeanesCite this: Anal. Chem. 1965, 37, 12, 1602–1604Publication Date (Print):November 1, 1965Publication History Published online1 May 2002Published inissue 1 November 1965https://doi.org/10.1021/ac60231a048RIGHTS & PERMISSIONSArticle Views1619Altmetric-Citations1488LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (350 KB) Get e-Alerts Get e-Alerts
Antigens recognized by autologous antibody in patients with renal-cell carcinoma (1999)

The screening of cDNA expression libraries derived from human tumors with autologous antibody (SEREX) is a powerful method for defining the structure of tumor antigens recognized by the humoral immune system. Sixty-five distinct antigens (NY-REN-1 to NY-REN-65) reactive with autologous IgG were identified by SEREX analysis of 4 renal cancer patients and were characterized in terms of cDNA sequence, mRNA expression pattern, and reactivity with allogeneic sera. REN-9, -10, -19, and -26 have a known association with human cancer. REN-9 (LUCA-15) and REN-10 (gene 21) map to the small cell lung cancer tumor suppressor gene locus on chromosome 3p21.3. REN-19 is equivalent to LKB1/STK11, a gene that is defective in Peutz-Jeghers syndrome and cancer. REN-26 is encoded by the bcr gene involved in the [t(9:22)] bcr/abl translocation. Genes encoding 3 of the antigens in the series showed differential mRNA expression; REN-3 displays a pattern of tissue-specific isoforms, and REN-21 and REN-43 are expressed at a high level in testis in comparison to 15 other normal tissues. The other 62 antigens were broadly expressed in normal tissues. With regard to immunogenicity, 20 of the 65 antigens reacted only with autologous sera. Thirty-three antigens reacted with sera from normal donors, indicating that their immunogenicity is not restricted to cancer. The remaining 12 antigens reacted with sera from 5-25% of the cancer patients but not with sera from normal donors. Seventy percent of the renal cancer patients had antibodies directed against one or more of these 12 antigens. Our results demonstrate the potential of the SEREX approach for the analysis of the humoral immune response against human cancer.
In Vitro and in Vivo Performance of Porcine Islets Encapsulated in Interfacially Photopolymerized Poly(Ethylene Glycol) Diacrylate Membranes (1999)

The usefulness of interfacial photopolymerization of poly(ethylene glycol) (PEG) diacrylate at a variety of concentrations and molecular weights to form hydrogel membranes for encapsulating porcine islets of Langerhans was investigated. The results from this study show in vitro and in vivo function of PEG-encapsulated porcine islets and the ability of PEG membranes to prevent immune rejection in a discordant xenograft model. Encapsulated islets demonstrated an average viability of 85% during the first week after encapsulation, slightly but significantly lower than unencapsulated controls. Encapsulated porcine islets were shown to be glucose responsive using static glucose stimulation and perifusion assays. Higher rates of insulin release were observed for porcine islets encapsulated in lower concentrations of PEG diacrylate (10-13%), not significantly reduced relative to unencapsulated controls, than were observed in islets encapsulated in higher concentrations (25%) of PEG diacrylate. Perifusion results showed biphasic insulin release from encapsulated islets in response to glucose stimulation. Streptozotocin-induced diabetic athymic mice maintained normoglycemia for up to 110 days after the implantation of 5,000-8,000 encapsulated porcine islet equivalents into the peritoneal cavity. Normoglycemia was also confirmed in these animals using glucose tolerance tests. PEG diacrylate-encapsulated porcine islets were shown to be viable and contain insulin after 30 days in the peritoneal cavity of Sprague-Dawley rats, a discordant xenograft model. From these studies, we conclude that PEG diacrylate encapsulation of porcine islets by interfacial photopolymerization shows promise for use as a method of xenoprotection toward a bioartificial endocrine pancreas.
A Low-Complexity Precoder for Large Multiuser MISO Systems (2008)

In this paper, we consider the problem of preceding in large multiuser MISO systems, where by 'large' we mean (i) large number of transmit antennas (N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> ) at the base station of the order of tens to hundreds of transmit antennas, and (ii) large number of downlink users (N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">u</sub> ) of the order of tens to hundreds of users where each user has one receive antenna. Such large MISO systems will be of immense interest because of the high capacities (sum-rates) of the order of hundreds of bits/channel use possible in such systems. We propose a vector perturbation based low-complexity precoder, termed as norm descent search (NDS) precoder, which has a complexity of just O(N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">u</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> ) per information symbol. This low complexity attribute of the precoder is achieved by searching for the perturbation vector over a reduced search space. Interestingly, in terms of BER performance, the proposed precoder achieves increasingly better BER for increasing N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> , N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">u</sub> , such that for large N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> , N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">u</sub> it achieves near-exponential diversity with some SNR loss, thus making it suited for large MISO systems both in terms of complexity as well as performance. The results of uncoded/turbo-coded simulations without and with channel estimation errors are presented.