gebhart/patrepeval huggingface dataset:
Recent Progress in Automatically Extracting Information from the Pharmacogenomic Literature (2010)

The biomedical literature holds our understanding of pharmacogenomics, but it is dispersed across many journals. In order to integrate our knowledge, connect important facts across publications and generate new hypotheses we must organize and encode the contents of the literature. By creating databases of structured pharmocogenomic knowledge, we can make the value of the literature much greater than the sum of the individual reports. We can, for example, generate candidate gene lists or interpret surprising hits in genome-wide association studies. Text mining automatically adds structure to the unstructured knowledge embedded in millions of publications, and recent years have seen a surge in work on biomedical text mining, some specific to pharmacogenomics literature. These methods enable extraction of specific types of information and can also provide answers to general, systemic queries. In this article, we describe the main tasks of text mining in the context of pharmacogenomics, summarize recent applications and anticipate the next phase of text mining applications.
Highly Activated Cytotoxic CD8 T Cells Express Protective IL-10 at the Peak of Coronavirus-Induced Encephalitis (2011)

Acute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. In this article, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10(+)CD8 and IL-10(-)CD8 T cells interconvert during acute disease, possibly based on recent Ag exposure. Strikingly, IL-10(+)CD8 T cells were more highly activated and cytolytic than IL-10(-)CD8 T cells, expressing greater levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Even though these cells are highly proinflammatory, IL-10 expressed by these cells was functional. Furthermore, IL-10 produced by CD8 T cells diminished disease severity in mice with coronavirus-induced acute encephalitis, suggesting a self-regulatory mechanism that minimizes immunopathological changes.
Prognostic and predictive role of tumour-associated macrophages in HER2 positive breast cancer (2019)

Disease outcomes of HER2+ breast cancers have dramatically improved after targeted therapies, such as trastuzumab became available. The main mechanism of action of trastuzumab depends on immunoactivation, while immunosuppressive tumour phenotype has been linked to adverse outcomes. Current study included metastatic HER2+ breast cancer patients treated with trastuzumab (n = 40). Immunohistochemistry was conducted to detect nitric oxide synthase 2 (iNOS) expressing M1 polarized and CD163<sup>+</sup> M2 polarized macrophages, FoxP3<sup>+</sup> regulatory T-cells (Tregs), CD47 and indoleamine 2,3-dioxygenase 1 (IDO1). High number of iNOS<sup>+</sup> M1-like macrophages, both in the center of the tumour (CT) and invasive margin (IM), was significantly associated with improved survival (p = 0.009) while high expression of IDO1 or CD47 in the malignant cells was associated with worsened prognosis (p = 0.018, p = 0.046). High number of CD163<sup>+</sup> M2-like macrophages in the CT, but not in the IM, and high number of FoxP3<sup>+</sup> Tregs in both locations showed non-significant tendencies towards poor prognosis. Moreover, high number of iNOS<sup>+</sup> M1-like macrophages combined with high number of CD8<sup>+</sup> T-cells in the CT was significantly associated with improved survival (p = 0.0003), and this combined marker predicted patient's ability to remain progression-free without trastuzumab after responding to the therapy (p = 0.003). Current study highlights the role of M1 polarized macrophages alone and in combination with CD8<sup>+</sup> cells in HER2+ breast cancer.
An Architecture for Differentiated Service (1998)

This document defines an architecture for implementing scalable service differentiation in the Internet. This architecture achieves scalability by aggregating traffic classification state which is conveyed by means of IP-layer packet marking using the DS field [DSFIELD]. Packets are classified and marked to receive a particular per-hop forwarding behavior on nodes along their path. Sophisticated classification, marking, policing, and shaping operations need only be implemented at network boundaries or hosts. Network resources are allocated to traffic streams by service provisioning policies which govern how traffic is marked and conditioned upon entry to a differentiated services-capable network, and how that traffic is forwarded within that network. A wide variety of services can be implemented on top of these building blocks.
3D object manipulation in a single photograph using stock 3D models (2014)

Photo-editing software restricts the control of objects in a photograph to the 2D image plane. We present a method that enables users to perform the full range of 3D manipulations, including scaling, rotation, translation, and nonrigid deformations, to an object in a photograph. As 3D manipulations often reveal parts of the object that are hidden in the original photograph, our approach uses publicly available 3D models to guide the completion of the geometry and appearance of the revealed areas of the object. The completion process leverages the structure and symmetry in the stock 3D model to factor out the effects of illumination, and to complete the appearance of the object. We demonstrate our system by producing object manipulations that would be impossible in traditional 2D photo-editing programs, such as turning a car over, making a paper-crane flap its wings, or manipulating airplanes in a historical photograph to change its story.
Birth and fertility rates for states by Hispanic origin subgroups: United States, 1990 and 2000. (2006)

This report presents U.S. and State-level data on births, birth rates, and fertility rates for Hispanic origin subgroups for 1990 and 2000. Data for non-Hispanic whites and non-Hispanic blacks are provided for comparison.Data are presented in detailed tables, graphs, and maps.Between 1990 and 2000, the total U.S. Hispanic population increased 58 percent, from 22,353,999 to 35,305,818. Over the same period of time, births to Hispanic mothers increased 37 percent, from 595,073 to 815,868. The smaller increases in births compared with the population resulted in a falling birth rate among Hispanic mothers (26.7 in 1990 to 23.1 births per 1,000 total population in 2000). Birth and fertility rates for Mexican, Puerto Rican, and Cuban mothers all fell between 1990 and 2000. Among the Hispanic subgroups, fertility rates in 2000 ranged from 105.1 births per 1,000 women aged 15-44 years for Mexican women to 49.3 for Cuban women. Differences in fertility exist not only between Hispanic subgroups but also within groups among States. For example, total fertility rates for Puerto Rican mothers, which estimates the number of children a group of 1,000 women will have in their lifetime, ranged in 2000 from 1,616.5 in New York to 2,403.0 in Pennsylvania.
Off-rate screening for selection of high-affinity anti-drug antibodies (2013)

The rapidly increasing number of therapeutic antibodies in clinical development and on the market requires corresponding detection reagents for monitoring the concentration of these drugs in patient samples and as positive controls for measurement of anti-drug antibodies. Phage display of large recombinant antibody libraries has been shown to enable the rapid development of fully human anti-idiotypic antibodies binding specifically to antibody drugs, since the in vitro panning approach allows for incorporation of suitable blockers to drive selection toward the paratope of the drug. A typical bottleneck in antibody generation projects is ranking of the many candidates obtained after panning on the basis of antibody binding strength. Ideally, such method will work without prior labeling of antigens and with crude bacterial lysates. We developed an off-rate screening method of crude Escherichia coli lysates containing monovalent Fab fragments obtained after phage display of the HuCAL PLATINUM® antibody library. We used the antibody drugs trastuzumab and cetuximab as antigen examples. Using the Octet® RED384 label-free sensor instrument we show that antibody off rates can be reliably determined in crude bacterial lysates with high throughput. We also demonstrate that the method can be applied to screening for high-affinity antibodies typically obtained after affinity maturation.
Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts (2013)

In abnormal skin wound healing, hypertrophic scars (HS) are characterized by excessive fibroblast hypercellularity and an overproduction of collagen, leading to atypical extracellular matrix (ECM) remodeling. Although the exact mechanisms of HS remain unclear, decreased HS fibroblast (HSFB) apoptosis and increased proliferation are evident in the development of HS. In this study, the contribution of the second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein (IAP)-binding protein with a low isoelectric point (pI) (Smac/DIABLO), an apoptosis-promoting protein released from the mitochondria, was investigated in human normal skin and HSFB cultures. The expression of Smac/DIABLO is usually decreased in many malignant tumors compared with normal tissues. Immunohistochemical analysis of skin tissues and the western blot analyses of fibroblasts revealed that the expression of Smac/DIABLO was lower in HS tissues compared with normal skin tissues. Of note, adenovirus-mediated Smac/DIABLO overexpression in the cultured HSFBs significantly reduced cell proliferation, as detected by the cell counting kit-8, and increased caspase-3 and -9 activity, as detected by spectrofluorimetry. In addition, it increased apoptosis, as detected by fluorescence-activated cell sorting (FACS). Furthermore, we found that the silencing of Smac with siRNA in the HSFBs induced a noticeable decrease in caspase-3 and -9 activity, leading to a significant reduction in apoptosis. In addition, the mRNA expression of type I and III pro-collagen detected in the HSFBs was significantly increased following the silencing of Smac with siRNA and was inhibited following Smac/DIABLO overexpression, as shown by real-time RT-PCR. In conclusion, Smac/DIABLO decreases the proliferation and increases the apoptosis of HSFBs. To our knowledge, the data from our study suggest for the first time that Smac/DIABLO is a novel therapeutic target for HS.
Cryptic primes (2004)

Prime numbers reserve a special place in number theory and computer science. Their extensive use in data structures, cryptography, nucleotide encoding, in developing musical tones and such merit their importance across all disciplines, especially in computer science. The article looks at the history and applications of primes, particularly their use in classical cryptographic systems, such as the Diffie-Hellman asymmetric-key cryptography algorithm and the RSA public key encryption system. Quantum cryptographic techniques are also discussed.
Portable, parallel 9-wavelength near-infrared spectral tomography (NIRST) system for efficient characterization of breast cancer within the clinical oncology infusion suite (2016)

A portable near-infrared spectral tomography (NIRST) system was developed with simultaneous frequency domain (FD) and continuous-wave (CW) optical measurements for efficient characterization of breast cancer in a clinical oncology setting. Simultaneous FD and CW recordings were implemented to speed up acquisition to 3 minutes for all 9 wavelengths, spanning a range from 661nm to 1064nm. An adjustable interface was designed to fit various breast sizes and shapes. Spatial images of oxy- and deoxy-hemoglobin, water, lipid, and scattering components were reconstructed using a 2D FEM approach. The system was tested on a group of 10 normal subjects, who were examined bilaterally and the recovered optical images were compared to radiographic breast density. Significantly higher total hemoglobin and water were estimated in the high density relative to low density groups. One patient with invasive ductal carcinoma was also examined and the cancer region was characterized as having a contrast ratio of 1.4 in total hemoglobin and 1.2 in water.
Identification of Novel Diagnostic Markers for Choroid Plexus Tumors (2006)

To identify specific markers for the diagnosis of choroid plexus tumors, gene expression profiles of choroid plexus epithelial cells (n = 8) and ependymal cells (n = 6) microdissected from human autopsy brains as well as choroid plexus papilloma tissue were investigated using DNA microarrays. Protein expression of genes overexpressed in choroid plexus was evaluated in normal choroid plexus, choroid plexus papilloma, choroid plexus carcinoma, other primary brain tumors, and cerebral metastases. Forty-six genes found to be overexpressed in normal choroid plexus epithelial cells were also present in choroid plexus papilloma. Among those, 11 were further analyzed by immunohistochemistry. Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases. Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases. Transthyretin stained choroid plexus (33 of 35), choroid plexus papilloma (14 of 18), and plexus carcinoma (2 of 5), but its specificity was significantly lower. Antibodies directed against coagulation factor V, glutathione peroxidase 3, pigment epithelium derived factor, serotonin receptor 5-HTR2C, lumican, fibulin-1, plastin-1, and cytokeratin 18 revealed varying degrees of specificity and sensitivity. Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors.
Evidence of an Enzymatic Source of Off Flavors in “Lipoxygenase‐Null” Soybeans (2008)

Abstract The utilization of soybean products as food ingredients and foods is often limited by their beany‐grassy flavor. Eliminating seed lipoxygenase (LOX) isozymes 1, 2 and 3 reduces the amounts of volatile off‐flavor compounds in stored soybeans and soy products significantly, but they are not completely eliminated. The present work presents evidence that lipoxygenase‐null (LOX‐null) soybeans contain a LOX‐like enzyme that is responsible for the off‐flavors in LOX‐null soybeans. Volatiles production in triple LOX‐null soybeans was terminated by heat treatment, which suggests an enzymatic cause to the off‐flavors. The source is LOX‐like in that the volatile compounds produced are similar to LOX‐generated products of polyunsaturated fatty acids. Oxygen was consumed when a LOX‐null protein solution was incubated with crude soybean oil suggesting that the enzyme catalyzed oxygen consuming reactions. The generation of flavor compounds was inhibited by the typical LOX inhibitors propyl gallate and nordihydroguaiaretic acid (NDGA). The enzyme appears to be more active with phosphatidylcholine than with other lipid substrates. The cause of the off‐flavors in LOX‐null beans appears to have enzyme‐like characteristics. This is the first report of the initial characterization of this LOX‐like enzyme.
Increased Glycosylation of Serum Human Chorionic Gonadotropin and Subunits from Eutopic and Ectopic Sources: Comparison with Placental and Urinary Forms* (1980)

The role of carbohydrate in the heterogeneity of hCG and its subunits is unclear. To study this question, we chromatographed over Sephadex G-100 an extract of term placenta as well as sera from a woman in the first and third trimesters of pregnancy and sera from two patients with nontrophoblastic malignancies. Samples were cochromatographed with radiolabeled urinary standards. hCG from first trimester pregnancy serum showed multiple peaks on G-100. The dominant peak eluted with an apparent molecular weight (72,000) higher than that of hCG from third trimester serum (63,000), urine (6),000), and placenta (59,000). hCG from both malignancy sera eluted with an apparent molecular weight (62,000) similar to that of hCG from third trimester and urinary hCG. Free hCG alpha from all sera eluted with a similar apparent molecular weight (29,000), which was higher than that of placental and urinary free alpha-subunit (22,000) and the alpha-subunit dissociated from intact hCG from all sources (22,000--23,000). The subunits were dissociated in the denaturing medium of 6 M guanidine-HCl, pH 3.0, and chromatographed in this medium over Sepharose CL-6B. This eliminated all of the differences in apparent molecular weight among corresponding forms that were found on G-100. All forms of hCG alpha coeluted with a chemically identified 80% deglycosylated hCG alpha. hCG and free alpha-subunits were incubated with mixed exoglycosidases which lacked detectable protease activity and were then rechromatographed on G-100. After deglycosylation, hCG from different sources eluted with a considerable heterogeneity (mol wt range, 40,000--50,000) not present in the native forms. Despite the heterogeneity of native free alpha-subunit from various sources, deglycosylation produced a common species with apparent molecular weights of 11,000--12,000, close to the chemically determined molecular weight of the polypeptide chain (10,400). These studies suggest that1) ectopic serum hCG and free alpha-subunit are similar to corresponding eutopic forms; 2) serum hCG and free alpha-subunit from all sources are more glycosylated than placental or urinary forms; 3) first trimester hCG is more glycosylated than other forms of hCG; and 4) serum free alpha-subunit is more glycosylated than the alpha-subunit which combines with hCG beta to form intact hCG.
Towards a questionnaire for measuring affective benefits and costs of communication technologies (2014)

As CSCW creates and investigates technologies for social communication, it is important to understand the emotional benefits and costs of these systems. We propose the Affec-tive Benefits and Costs of Communication Technologies (ABCCT) questionnaire to supplement traditional qualita-tive methods of understanding communication media. We discuss the pilots of this survey with 45 children and 110 adults measuring the inter-item reliability of this instru-ment. We present the results of interviews with 14 children and 14 adults, which help confirm that the ABCCT measures the same constructs that may emerge through interview investigations. Finally, we demonstrate that the ABCCT is sensitive enough to discriminate between differ-ent communication technologies and has shown promise in some of its early adoption. Though the ABCCT is not with-out limitations, it may provide a way to compare technolo-gies in field deployments, draw findings across investiga-tions, and quantify the impact of specific design decisions.
‘‘Homologous restriction’’ in complement lysis: roles of membrane complement regulators (2005)

The complement system is a powerful bactericidal immune defence with the potential to damage self cells. Protection of self is provided by expression on cells of a battery of membrane regulators that inhibit activation of complement. Roles of complement in the rejection of transplanted organs have long been recognized, and are particularly relevant in xenotransplantation, where hyperacute rejection is complement-driven. Inhibiting complement was therefore considered early in the history of xenografting, and the use of membrane complement regulators to this end was proposed more than two decades ago. For each of the membrane regulators in humans, early studies implied a species-specificity of action, inhibiting human complement but not that from other species. The dogma of species-specificity dictated strategies for inhibiting complement in xenografts and drove the creation of donor transgenic pigs expressing human regulators. Here we critically evaluate the evidence for species-specificity in membrane complement regulators from humans and other animals. We challenge the dogma and show that there is considerable cross-species activity for each of the membrane regulators of complement. Acceptance of the fact that species selectivity is not a limitation will open new avenues for protection of the xenograft from complement damage.
On the Immobilization of Ruthenium Metathesis Catalysts in Imidazolium Ionic Liquids (2009)

New ionophilic Hoveyda-type complexes were prepared by the treatment of Grubbs' second-generation catalyst with the readily obtained 2,3-dimethyl-1-[1-methyl-3-(2-vinylphenoxy)butyl]imidazolium hexafluorophosphate ligand, for example. This new carbene complex immobilized in BMI·PF6 ionic liquid presents excellent catalytic activities in 1,7-octadiene, diallyl diethylmalonate, and allylmethallyl dimethylmalonate ring-closing metathesis (RCM) reactions. The ionophilic complex can be recycled up to seven times in the 1,7-octadiene RCM reaction. The structure of this complex has been unambiguously established by NMR and single-crystal X-ray diffraction studies.
Stabilization of an isolated helical capping box in solution by hydrophobic interactions: Evidence from the NMR study of bioactive peptides from the C-terminus of human C5a anaphylatoxin (1996)

Synthetic analogues of the C-terminal portion of C5a were designed and found to be agonists of the C5a receptor [J. A. Ember et al. (1992) Jounral of Immunology, Vol. 148, p. 3165]. Nuclear magnetic resonance experiments were carried out to determine the solution conformation of the most potent analogue, the peptide C5a 65-74 (Tyr65, Phe67) (Tyr65-Ser66-Phe67-Lys68-Asp69-Met70 -Gln71- Leu72-Gly73-Arg74). Medium-range nuclear Overhauser effects (NOEs) were observed for residues 65-70 of this C5a peptide, suggesting that this region adopts a folded conformation in a significant population of the solution conformational ensemble. Quantitative analyses of (3)J(NH-alphaH) coupling constants and sequential NOE cross peaks gave an estimated helical population of 65% in the region Ser66-Met70. Additional evidence supporting the presence of a helical turn includes reduced amide-proton temperature coefficients and lowered (3)J(NH-alphaH) coupling constants in the region of Phe67-Met70. Conformational behavior of this C5a analogue peptide was studied using molecular modeling incorporating observed NOEs as constraints. The side chains of Tyr65, Phe67, and Met70 consistently form a hydrophobic cluster in all the model structures. The side chains of residues Ser66 and Asp69 can form reciprocal hydrogen bonds with the backbone NH groups of these two residues, indicating that residues Ser66-Phe67-Lys68-Asp69 (or SFKD) form a helix-stabilizing capping box (E. T. Harper and G. D. Rose (1993) Biochemistry, Vol. 32, p. 7605; H. X. Zhou et al. (1994) Proteins: Structure, Function and Genetics, Vol. 18, p. 1] even within the single turn of helical structure found in the analogue C5a peptide. A comparison of nmr results obtained for the analogue peptide and the natural decapeptide C5a 65-74 (Ile65-Ser66-His67-Lys68-Asp-69- Met70-Gln71-Leu72-Gly73-Arg74) indicated that incorporation of residues Tyr65 and Phe67 helps stabilize an isolated capping box involving residues Ser66-Asp69 in the C5a peptides through more extensive hydrophobic/aromatic interactions between residues Tyr65, Phe67, and Met70 in the analogue peptide C5a 65-74 (Tyr65, Phe67). These results constitute the first experimental demonstration of hydrophobic determinants in helical capping-box interactions, proposed recently by a statistical analysis of protein structures [J. W. Seale et al. (1994) Protein Science, Vol. 3, pp. 1741-1745]. The stabilized helical turn may also account for the greater potency of the analogue peptide C5a65-74 (Tyr65, Phe67) in receptor-binding assays.