gebhart/patrepeval huggingface dataset:
Study of Interlaboratory Reliability and Reproducibility of Estrogen and Progesterone Receptor Assays in Europe (2001)

Immunohistochemical assays for estrogen receptors (ERs) and progesterone receptors (PRs) have not been surveyed for technical validity. In the present study, the reliability of the immunohistochemical assay for ER and PR was evaluated using data from 105 laboratories participating in external quality assessment (EQA) during a 2-year period. Technical variables associated with reliable immunostaining were analyzed. The efficiency of the antigen retrieval step was identified as the single most important contributory factor influencing the overall reproducibility of the assays. Reliable assays were found in 24 (36%) of 66 laboratories participating in continual EQA, including the majority of centers known to have clinically validated results. Inadequate assay sensitivity, with subsequent weak staining, was the main cause of poor and variable results by laboratories using microwave antigen retrieval; too short a heating time was identified as the principal contributory factor. Extension of the heating time resulted in significant improvement regardless of all other variables in the immunohistochemical protocol. Continual participation in EQA is an effective means for identifying and ameliorating variables that influence the reliability of immunohistochemical assays for predictive markers, thereby assisting in technical validation and standardization.
Lithium Concentration Dependent Elastic Properties of Battery Electrode Materials from First Principles Calculations (2014)

This paper aims to help fill a gap in the literature on Li-ion battery electrode materials due to the absence of measured elastic constants needed for diffusion induced stress models. By examining results from new first principles density functional theory (DFT) calculations of LiCoO2, LiMn2O4, (and their delithiated hosts, CoO2 and MnO2), LixAl alloys, and data from the extant literature on LiFePO4 (and FePO4), LiTi2O4 (and Li2Ti2O4), LixSi, LixSn and lihtium graphite-interaction-compounds, a compelling picture emerges on the dependency of the elastic properties on Li concentration. Specifically, three distinct categories of behavior are found: (a) the averaged Young's moduli change very minimally upon lithiation of the spinel and olivine structures; (b) lithiation induced stiffening is observed only when new and stronger bonds between the Li ions and the host materials are formed in layered compounds; and (c) for alloy-forming electrode materials, such as Si, β-Sn and Al, the averaged Young's moduli of lithiated compounds follow the linear rule of mixtures. The tendency of ductile or brittle behavior electrode materials is investigated with the Pugh criterion, and a ductile to brittle transition was found to occur during lithiation of Al and β-Sn, but not in Si.
Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum (2005)

The study examines the preponderance and mechanism of mammalian target of rapamycin (mTOR) activation in three distinct types of transformed B lymphocytes that differ in expression of the EBV genome. All three types [EBV-immortalized cells that express a broad spectrum of the virus-encoded genes (type III latency; EBV+/III), EBV-positive cells that express only a subset of the EBV-encoded genes (EBV+/I), and EBV-negative, germinal center-derived cells (EBV-)] universally displayed activation of the mTOR signaling pathway. However, only the EBV+/III transformed B cells displayed also activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway that is considered to be the key activator of mTOR and of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway that coactivates one of the immediate targets of mTOR, p70 S6K1. Activation of the PI3K/Akt and MEK/ERK, but not of the mTOR pathway, was inhibited by serum withdrawal and restored by insulin growth factor-I. In contrast, activation of mTOR, but not PI3K/Akt and MEK/ERK, was sensitive to nutrient depletion. Both direct Akt (Akt inhibitors I-III) and a PI3K inhibitor (wortmannin at 1 nmol/L) suppressed Akt phosphorylation without significantly affecting mTOR activation. Furthermore, rapamycin, a potent and specific mTOR inhibitor, suppressed profoundly proliferation of cells from all three types of transformed B cells. U0126, a MEK inhibitor, had a moderate antiproliferative effect only on the EBV+/III cells. These results indicate that mTOR kinase activation is mediated in the transformed B cells by the mechanism(s) independent of the PI3K/Akt signaling pathway. They also suggest that inhibition of mTOR signaling might be effective in therapy of the large spectrum of B-cell lymphomas.
Spherical, rolling magnet generators for passive energy harvesting from human motion (2009)

In this work, non-resonant, vibrational energy harvester architectures intended for human-motion energy scavenging are researched. The basic design employs a spherical, unidirectionally magnetized permanent magnet (NdFeB) ball that is allowed to move arbitrarily in a spherical cavity wrapped with copper coil windings. As the ball rotates and translates within the cage, the time-varying magnetic flux induces a voltage in the coil according to Faraday's Law. Devices ranging from 1.5 cm3 to 4 cm3 in size were tested under human activity scenarios—held in the user's hand or placed in the user's pocket while walking (4 km h−1) and running (14.5 km h−1). These harvesters have demonstrated rms voltages ranging from ∼80 mV to 700 mV and time-averaged power densities up to 0.5 mW cm−3.
Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells. (2002)

Factors that aid survival of prostate cancer cells in the presence of the various categories of cytotoxic cytokines present in tumors in vivo are largely unknown. Osteoprotegerin (OPG) is a decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that inhibits TRAIL-induced apoptosis. In relation to this activity, we hypothesized that the ability to produce OPG by prostate cancer cells would confer a survival advantage on these cells. In this study we have demonstrated that high levels of OPG are produced by the hormone-insensitive prostate cancer cell lines PC3 and Du145, whereas the hormone-sensitive cell line LNCaP produced 10-20-fold less OPG under the same conditions. A strong negative correlation was observed between levels of endogenously produced OPG in the medium and the capacity of TRAIL to induce apoptosis in cells that produced high levels of OPG. The antiapoptotic effect of OPG was reversed by coadministration of 100-fold molar excess of receptor-activator of nuclear factor-kappaB ligand, another protein that selectively binds OPG. These observations suggest that prostate cancer-derived OPG may be an important survival factor in hormone-resistant prostate cancer cells.
Bacterial expression, purification and preliminary kinetic description of the kinase domain of v-fps (1995)

The gene coding for the tyrosine protein kinase domain of v-fps was subcloned into a plasmid vector expressing glutathione-S-transferase (GST). This new vector expresses a fusion protein in Escherichia coli composed of the kinase domain linked with GST at the N-terminus (GST-kin). A portion of the total expressed protein was soluble upon cell lysis and was purified by affinity chromatography using glutathione cross-linked agarose. GST-kin (M(r) 57,000) is a phosphoprotein as judged by 32P autoradiography, consistent with the known autophosphorylation site within the kinase core [Weinmaster et al. (1984) Cell, 37, 559-568]. Cleavage of the fusion protein with thrombin and purification on phosphocellulose resin yielded the pure kinase domain (M(r) 33,000). The activity of the kinase domain is indistinguishable from that of GST-kin using the peptide substrate EEEIYEEIE, indicating that N-terminal fusion has no effect on the kinase domain. GST-kin phosphorylates a second peptide, EAEIYEAIE, with improved catalytic efficiency. Initial velocity data are consistent with a random bireactant mechanism with no substrate synergism observed in the ternary complex. Steady-state kinetic analyses reveal that this peptide is phosphorylated, with a kcat of 3.6 s-1, a Kpeptide of 500 microM and a KATP of 250 microM. The expression, purification and preliminary kinetic analysis of the kinase domain of v-fps provide the first step in the application of structure-function studies for this oncoprotein.
Electron Resonant Tunneling Through InAs∕GaAs Quantum Dots Embedded in a Schottky Diode with an AlAs Insertion Layer (2006)

Molecular beam epitaxy was employed to manufacture self-assembled quantum dot Schottky resonant tunneling diodes. By virtue of a thin insertion barrier, the thermal current was effectively reduced and electron resonant tunneling through quantum dots under both forward and reverse biased conditions was observed at relatively high temperature of . The ground states of quantum dots were found to be at below the conduction band of matrix. The theoretical computations were in conformity with experimental data.
Three-Dimensional Structure of a Recombinant Gap Junction Membrane Channel (1999)

Gap junction membrane channels mediate electrical and metabolic coupling between adjacent cells. The structure of a recombinant cardiac gap junction channel was determined by electron crystallography at resolutions of 7.5 angstroms in the membrane plane and 21 angstroms in the vertical direction. The dodecameric channel was formed by the end-to-end docking of two hexamers, each of which displayed 24 rods of density in the membrane interior, which is consistent with an alpha-helical conformation for the four transmembrane domains of each connexin subunit. The transmembrane alpha-helical rods contrasted with the double-layered appearance of the extracellular domains. Although not indicative for a particular type of secondary structure, the protein density that formed the extracellular vestibule provided a tight seal to exclude the exchange of substances with the extracellular milieu.
Selective 2′-benzoylation at the 2′, 3′-diols of protected ribonucleosides. New solid phase synthesis of RNA and DNA-RNA mixtures (1982)

5'-0-(Dimethoxytrityl)-2'-0-(benzoyl or 3,4,5-trimethoxybenzoyl)-base protected ribonucleosides have been prepared by selective benzoylation of the 2'-hydroxyl group. The isomerization of the 2'-benzoates to the 3'-benzoates was studied. The protected ribonucleosides have been converted to either methylphosphochloridites or methylphosphoamidites and used to synthesize oligoribonucleotides on silica gel solid support. The synthetic RNA were deprotected and isolated using conditions that minimize internucleotide cleavage. The use of 2'-benzoates as protecting groups for ribonucleosides has made it possible to easily prepare and isolate mixtures of DNA and RNA.
Origin and Pathogenesis of Pelvic (Ovarian, Tubal, and Primary Peritoneal) Serous Carcinoma (2013)

A new paradigm for the pathogenesis of female pelvic cancer helps explain persistent problems in describing the development and diverse morphology of these neoplasms. This paradigm incorporates recent advances in the molecular pathogenesis of epithelial ovarian cancer (EOC) with new insights into the origin of these tumors. Correlated clinicopathologic and molecular genetic studies gave rise to a dualistic model that divides the various histologic types of EOCs into two broad categories designated type I and type II. Because serous carcinomas are the most common EOC and account for the vast majority of deaths, they form the subject of this review. Recent studies indicate that the precursor of ovarian high-grade serous carcinoma appears to develop from an occult intraepithelial carcinoma in the fimbria of the fallopian tube and involves the ovary secondarily. Another possible mechanism is implantation of normal fimbrial epithelium on the denuded ovarian surface at the site of rupture when ovulation occurs, causing the development of cortical inclusion cysts. The dualistic model serves as a framework for the study of ovarian cancer and can help investigators organize this complex group of neoplasms. It also facilitates the development of novel approaches to prevention, screening, and treatment of this devastating disease.
Adipocyte metabolism in adipocyte fatty acid binding protein knockout mice (aP2-/-) after short-term high-fat feeding: functional compensation by the keratinocyte [correction of keritinocyte] fatty acid binding protein. (2000)

Mice null for adipocyte fatty acid binding protein (AFABP) compensate by increasing expression of keratinocyte fatty acid binding protein (KFABP) (Hotamisligil et al. Science 274:1377-1379, 1996). In the present study, AFABP knockout (KO) and wild-type (WT) mice became equally obese on a high-fat diet, as judged by fat pad weights, adipocyte size, and body composition analysis. High-fat feeding led to moderate insulin resistance in both WT and AFABP knockout mice, as indicated by an approximately 2-fold increase in plasma insulin. However, in the high fat-fed mice, plasma glucose levels were approximately 15% lower in the AFABP-KO mice. Adipocytes isolated from AFABP-KO and WT mice fed high- or low-fat diets exhibited similar rates of basal and norepinephrine-stimulated lipolysis and insulin-stimulated rates of glucose conversion to fatty acids and glyceride-glycerol. However, basal glucose conversion to fatty acids was higher in adipocytes of AFABP-KO mice. Adipocyte tumor necrosis factor-alpha release was similarly increased by high-fat diet-induced obesity in both WT and AFABP-KO mice. As assessed by Western blot analysis, the level of KFABP protein in AFABP-KOs was approximately 40% of the level of AFABP in WT controls. The binding affinities of KFABP for long-chain fatty acids were 2- to 4-fold higher than those of AFABP, but the relative affinities for different fatty acids were similar. As for AFABP, the rate of fatty acid transfer from KFABP to model phospholipid vesicles was increased with acceptor membrane concentration and by inclusion of acidic phospholipids, indicating a similar mechanism of transfer. We conclude KFABP can functionally compensate for the absence of AFABP, resulting in no major alterations in adipocyte metabolism or fat accumulation in response to short-term feeding of high-fat diets that result in moderate hyperinsulinemia.
IP 7 Debut in Insulin Release (2007)

An inositol compound determines the capacity of the pancreas to release insulin and may function similarly in other secretory cells.
ST8Sia II and ST8Sia IV Polysialyltransferases Exhibit Marked Differences in Utilizing Various Acceptors Containing Oligosialic Acid and Short Polysialic Acid (2002)

Polysialylation of the neural cell adhesion molecule (NCAM) is thought to play a critical role in neural development. Two polysialyltransferases, ST8Sia II and ST8Sia IV, play dominant roles in polysialic acid synthesis on NCAM. However, the individual roles and mechanisms by which these two enzymes form large amounts of polysialic acid on NCAM were heretofore unknown. Previous studies indicate that ST8Sia IV forms more highly polysialylated N-glycans on NCAM than ST8Sia II in vitro. In the present study, we first demonstrated that a combination of ST8Sia II and ST8Sia IV cooperatively polysialylated NCAM, resulting in NCAM N-glycans containing more, and thus longer, polysialic acid than when the enzymes were used individually. There was also an increase in polysialylated NCAM when we used ST8Sia II and ST8Sia IV sequentially, whereas there appeared to be a subtle increase when the enzymes were used in the reverse order. Furthermore, ST8Sia IV was able to add polysialic acid to oligosialylated oligosaccharides and unpolysialylated antennas in N-glycans attached to NCAM, even when polysialic acid was attached to at least one of the other antennas. By contrast, ST8Sia II added little polysialic acid to the same acceptors. On the other hand, neither ST8Sia II nor ST8Sia IV could add polysialic acid to a polysialylated antenna of NCAM N-glycans. These combined results indicate that the synergistic effect of ST8Sia II and ST8Sia IV is caused by: 1) the ability of ST8Sia IV to add polysialic acid to oligosialic acid formed by ST8Sia II, 2) the potential of ST8Sia IV to act on more antennas of N-glycans than ST8Sia II, and 3) the ability of ST8Sia II and ST8Sia IV in combination to act on the fifth and sixth N-glycosylation sites of NCAM.
Mouse Antibodies to Human Zona Pellucida: Evidence that Human ZP3 is Strongly Immunogenic and Contains Two Distinct Isomer Chains1 (1990)

Polyclonal antibodies were raised in mice by immunization with solubilized human zonae pellucidae (ZP). Dot-blot analysis and ELISAs showed very strong immunoreactivity against human and pig ZP, and less immunoreactivity against rabbit and mouse ZP. One- and two-dimensional (1D and 2D) Western blot analysis detected immunoreactivity to three human ZP-specific bands. Under 1D nonreducing conditions, bands were detected at Mr 97,000, 61,000, and 51,000; the lower molecular weight (MW) bands showed the strongest reaction. Three acidic bands were detected under nonreducing 2D Western blot analysis, one at Mr 85,000-107,000, and two closely apposed, parallel, and more acidic bands at Mr 47,000-55,000 and Mr 55,000-62,000. The lower MW bands displayed considerable microheterogeneity, with 8-13 charge isomers detected; the lower MW form (ZP3L) appeared to be more strongly reactive than the higher MW form (ZP3H), and displayed a more intense labeling towards the basic end of the isomer charge train. The human ZP antiserum detected electrophoretically separated heterologous ZP from pigs, rabbits, and mice, and was also shown to inhibit homologous sperm-zona binding in in vitro assays. This is the first study to report that human ZP3 consists of two distinct isomer chains.
Abstract 3825: INCAGN02390, a novel antagonist antibody that targets the co-inhibitory receptor TIM-3 (2018)

Abstract Unprecedented rates of durable clinical responses have been observed for antibody-based therapeutics targeting immune checkpoint proteins such as cytotoxic T lymphocyte antigen-4 (CTLA-4) or programmed death receptor-1 (PD-1). Nonetheless, a significant number of patients experience de novo resistance or relapse due to adaptive resistance mechanisms. T-cell immunoglobulin and mucin domain containing-3 (TIM-3) is an inhibitory receptor involved in immune tolerance often co-opted by tumors to prevent successful antitumor responses. Accordingly, TIM-3 is frequently expressed on myeloid and so-called exhausted T and NK cells within the tumor microenvironment. Targeting the TIM-3 pathway in preclinical models has provided additional rationale for pharmacologic modulation of this axis in cancer patients. INCAGN02390 is a novel and fully human Fc-engineered IgG1κ antibody developed to antagonize the TIM-3 pathway for the treatment of human malignancies. INCAGN02390 forms a high-affinity interaction with TIM-3, occluding access to the CC'-FG binding cleft and blocking phosphatidylserine binding. In addition, INCAGN02390 elicits rapid receptor internalization, potentially obviating interactions with other described or undescribed ligands. INCAGN02390 also enhances IFN-γ production from T cells undergoing tonic TCR stimulation when combined with PD-1 blockade. Finally, to demonstrate combinatorial potential, we show potent antitumor activity of an anti-mouse TIM-3 antibody in concert with other checkpoint antibodies in vivo. In summary, these data support assessment of INCAGN02390 in patients with advanced or metastatic solid tumors. Citation Format: Jeremy Waight, Priyadarshini Iyer, Ekaterina Breous-Nystrom, Christina Riordan, Mark Findeis, Dennis Underwood, Joseph Connolly, Michele Sanicola-Nadel, Horacio Nastri, Peggy Scherle, Gregory Hollis, Reid Huber, Robert Stein, Mark van Dijk, Nicholas S. Wilson. INCAGN02390, a novel antagonist antibody that targets the co-inhibitory receptor TIM-3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3825.
Periodontal Regeneration with a Combination of Enamel Matrix Proteins and Autogenous Bone Grafting (2003)

The combination of enamel matrix derivative plus autogenous bone graft stimulated statistically significant periodontal regeneration in the more narrow 1 and 2 mm lesions. No statistically significant difference was observed in the wider 4 and 6 mm lesions. In many cases, dramatic amounts of new cementum, Sharpey's fibers, periodontal ligament, and bone tissue were formed far above the notch placed at the base of the contaminated defects. This was especially significant considering the width of some of the defects and the fact that no oral hygiene was performed over the 5-month healing period. This periodontal regeneration occurred in the absence of exogenous growth factors or barrier membranes. In summary, the combination of enamel matrix derivative and autogenous bone represents a therapeutic combination that can be highly effective in stimulating significant amounts of periodontal regeneration.
Insulin Action and the Insulin Signaling Network* (1995)

IN THE fasted state, glucose homeostasis depends upon the balance between hepatic glucose production and glucose utilization by the major insulin-dependent tissues, such as liver, adipose, and muscle, and by insulin-independent tissues, such as brain and kidney. This balance is tightly regulated by pancreatic hormones. Thus, in normal individuals, the response to increased plasma glucose levels is an increase in secretion of insulin from β-cells of the pancreatic islets. This increase in circulating insulin levels stimulates glucose transport into peripheral tissues and inhibits hepatic gluconeogenesis. In type II diabetes there are at least two fundamental defects: one is a decrease in the ability of peripheral tissues to respond to insulin (insulin resistance), and the second is impaired β-cell function, which results from long-term hyperglycemia. It appears that both genetic and environmental factors are responsible for the progression from normal glucose tolerance to type II diabetes (1–4). In addition to its primary effects on glucose homeostasis, insulin also promotes a number of other cellular events including regulation of ion and amino acid transport, lipid metabolism, glycogen synthesis, gene transcription and mRNA turnover, protein synthesis and degradation, and DNA synthesis (Fig. 1). Thus the actions of insulin play key roles in the normal storage of ingested fuels and in normal cellular growth and differentiation. The biological importance of these effects of insulin are most obvious in the uncontrolled type I diabetic in ketoacidosis (1, 3–5). To fully understand the events leading to insulin-resistant states and the pathophysiology of insulin deficiency, it is necessary to identify, at the molecular level, the key components in the insulin-signaling pathway.