gebhart/patrepeval huggingface dataset:
Androgen treatment in women (1999)

Many women, both before and after menopause, may have symptoms of androgen deficiency: unexplained fatigue, lack of well-being and diminished libido. If plasma levels of bioavailable testosterone are low, these symptoms will mostly be relieved by judicious administration of testosterone. The addition of testosterone to postmenopausal hormone replacement regimens is becoming more widespread, and other potential uses include prevention and treatment of bone loss, treatment of spontaneous or iatrogenic androgen deficiency in premenopausal women, and, possibly, management of the premenstrual syndrome.
Inhibition of gene expression in human cells through small molecule-RNA interactions (1999)

Small molecules that bind their biological receptors with high affinity and selectivity can be isolated from randomized pools of combinatorial libraries. RNA-protein interactions are important in many cellular functions, including transcription, RNA splicing, and translation. One example of such interactions is the mechanism of trans-activation of HIV-1 gene expression that requires the interaction of Tat protein with the trans-activation responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5' end of all nascent HIV-1 transcripts. Here we demonstrate the isolation of small TAR RNA-binding molecules from an encoded combinatorial library. We have made an encoded combinatorial tripeptide library of 24,389 possible members from D-and L-alpha amino acids on TentaGel resin. Using on-bead screening we have identified a small family of mostly heterochiral tripeptides capable of structure-specific binding to the bulge loop of TAR RNA. In vitro binding studies reveal stereospecific discrimination when the best tripeptide ligand is compared with diastereomeric peptide sequences. In addition, the most strongly binding tripeptide was shown to suppress transcriptional activation by Tat protein in human cells with an IC(50) of approximately 50 nM. Our results indicate that tripeptide RNA ligands are cell permeable, nontoxic to cells, and capable of inhibiting expression of specific genes by interfering with RNA-protein interactions.
Transcriptome and Proteome Analysis ofBacillus subtilisGene Expression Modulated by Amino Acid Availability (2002)

A comprehensive study of Bacillus subtilis gene expression patterns in response to amino acid availability was performed by means of proteomics and transcriptomics. The methods of two-dimensional protein gel electrophoresis and DNA macroarray technology were combined to analyze cells exponentially grown in minimal medium with and without 0.2% Casamino Acids (CAA). This approach revealed about 120 genes predominantly involved in amino acid biosynthesis, sporulation, and competence, which were downregulated in CAA-containing medium. Determination of sporulation frequencies confirmed the physiological relevance of the expression data.
FORMATION AND FUNCTION OF SPEMANN'S ORGANIZER (1997)

The organizer is formed in an equatorial sector of the blastula stage amphibian embryo by cells that have responded to two maternal agents: a general mesoendoderm inducer (involving the TFG-beta signaling pathway) and a dorsal modifier (probably involving the Wnt signaling pathway). The meso-endoderm inducer is secreted by most vegetal cells, those containing maternal materials that had been localized in the vegetal hemisphere of the oocyte during oogenesis. As a consequence of the inducer's distribution and action, the competence domains of prospective ectoderm, mesoderm, and endoderm are established in an animal-to-vegetal order in the blastula. The dorsal modifier signal is secreted by a sector of cells of the animal and vegetal hemispheres on one side of the blastula. These cells contain maternal materials transported there in the first cell cycle from the vegetal pole of the egg along microtubules aligned by cortical rotation. The Nieuwkoop center is the region of blastula cells secreting both maternal signals, and hence specifying the organizer in an equatorial sector. Final steps of organizer formation at the late blastula or early gastrula stage may involve locally secreted zygotic signals as well. At the gastrula stage, the organizer secretes a variety of zygotic proteins that act as antagonists to various members of the BMP and Wnt families of ligands, which are secreted by cells of the competence domains surrounding the organizer. BMPs and Wnts favor ventral development, and cells near the organizer are protected from these agents by the organizer's inducers. The nearby cells are derepressed in their inherent capacity for dorsal development, which is apparent in the neural induction of the ectoderm, dorsalization of the mesoderm, and anteriorization of the endoderm. The organizer also engages in extensive specialized morphogenesis, which brings it within range of responsive cell groups. It also self-differentiates to a variety of axial tissues of the body.
An Analysis of Autoimmunity through Studies of DNA Antibody Idiotypes (1988)

The existence of idiotypic networks, first postulated over 12 years ago, is now widely recognised. Idiotypic analyses of autoantibodies have been reported among both hybridoma-derived and naturally occurring immunoglobulins. In this review the many studies of idiotypes detected on anti-DNA antibodies, notably one designated 16/6, are analysed to see what clues they offer to our understanding of autoimmunity. The links between infection and autoimmunity are emphasised by this analysis. It is also obvious that idiotypes first identified an autoantibodies are not confined to these immunoglobulins. Thus, the 16/6 idiotype originally described on a hybridoma-derived monoclonal anti-DNA antibody has also been identified on naturally occurring antibodies binding the Klebsiella polysaccharide K30.
Roles of the cytoplasmic and transmembrane domains of syntaxins in intracellular localization and trafficking (2001)

Syntaxins are target-soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (t-SNAREs) involved in docking and fusion of vesicles in exocytosis and endocytosis. Many syntaxin isoforms have been isolated, and each one displays a distinct intracellular localization pattern. However, the signals that drive the specific intracellular localization of syntaxins are poorly understood. In this study, we used indirect immunofluorescence analysis to examine the localization of syntaxin chimeras, each containing a syntaxin transmembrane domain fused to a cytoplasmic domain derived from a different syntaxin. We show that the cytoplasmic domains of syntaxins 5, 6, 7 and 8 have important effects on intracellular localization. We also demonstrate that the transmembrane domain of syntaxin 5 is sufficient to localize the chimera to the compartment expected for wild-type syntaxin 5. Additionally, we find that syntaxins 6, 7 and 8, but not syntaxin 5, are present at the plasma membrane, and that these syntaxins cycle through the plasma membrane by virtue of their cytoplasmic domains. Finally, we find that di-leucine-based motifs in the cytoplasmic domains of syntaxins 7 and 8 are necessary for their intracellular localization and trafficking via distinct transport pathways. Combined, these results suggest that both the cytoplasmic and the transmembrane domains play important roles in intracellular localization and trafficking of syntaxins.
Synthesis, Structural Characterization, and Solution Behavior of the First Mononuclear, Aqueous Aluminum Citrate Complex (1999)

The significance of the interaction between aluminum and citrate in biological media is exemplified by the synthesis, isolation, structural characterization, and solution behavior of the first mononuclear aluminum citrate complex. The chemical and structural features of the low molecular weight aluminum citrate species characterized help gain insight into citrate's ability, as a natural ligand, to enhance aluminum's absorption and thus affect its accumulation and biotoxicity at biological sites.
Effect of in vitro culture of human embryos on birthweight of newborns (2010)

In vitro culture of human embryos can affect birthweight of live born singletons.
Whole-exome sequencing in adult ETP-ALL reveals a high rate of DNMT3A mutations (2013)

Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) is a high-risk subgroup of T-lineage ALL characterized by specific stem cell and myeloid features. In adult ETP-ALL, no comprehensive studies on the genetic background have been performed to elucidate molecular lesions of this distinct subgroup. We performed whole-exome sequencing of 5 paired ETP-ALL samples. In addition to mutations in genes known to be involved in leukemogenesis (ETV6, NOTCH1, JAK1, and NF1), we identified novel recurrent mutations in FAT1 (25%), FAT3 (20%), DNM2 (35%), and genes associated with epigenetic regulation (MLL2, BMI1, and DNMT3A). Importantly, we verified the high rate of DNMT3A mutations (16%) in a larger cohort of adult patients with ETP-ALL (10/68). Mutations in epigenetic regulators support clinical trials, including epigenetic-orientated therapies, for this high-risk subgroup. Interestingly, more than 60% of adult patients with ETP-ALL harbor at least a single genetic lesion in DNMT3A, FLT3, or NOTCH1 that may allow use of targeted therapies.
Driver drowsiness detection using the in-ear EEG (2016)

Driver drowsiness monitoring is one of the most demanded technologies for active prevention of severe road accidents. Electroencephalogram (EEG) and several peripheral signals have been suggested for the drowsiness monitoring. However, each type of signal has partial limitations in terms of either convenience or accuracy. Recent emerged concept of in-ear EEG raises expectations due to reduced obtrusiveness. It is yet unclear whether the in-ear EEG is effective enough for drowsiness detection in comparison with on-scalp EEG or peripheral signals. In this work, we evaluated performance of the in-ear EEG in drivers' alertness-drowsiness classification for the first time. Simultaneously, we also tested three peripheral signals including electrocardiogram (ECG), photoplethysmogram (PPG), and galvanic skin response (GSR) which have advantage in convenience of measurement. The classification analysis using the in-ear EEG resulted in high classification accuracy comparable to that of the individual on-scalp EEG channels. The ECG, PPG and GSR showed competitive performance but only when used together in pairwise combinations. Our results suggest that the in-ear EEG would be viable alternative to the single channel EEG or the individual peripheral signals for the drowsiness monitoring.
Infrared light utilized for photodynamic therapy by activation of rare earth phosphors for visible light generation (2007)

Introduction: Photodynamic therapy (PDT) is a treatment for cancer requiring activation of a photosensitizer for light-mediated tumor cytotoxicity. PDT is limited by tissue penetration because visible light is required for photosensitizer activation. Sunstones<sup>TM</sup> are rare-earth phosphors which up-convert energy from infrared wavelengths to emit higher energy in the visible spectrum. We utilized this unique characteristic to generate light of appropriate intensity and wavelength for photosensitizer activation and subsequent tumor cell eradication. Methods: Sunstones<sup>TM</sup> with infrared absorption at 808 and 980nm and visible two-photon emission at 549.9 and 663.1nm were used. A murine NSCLC line was used to determine <i>in vitro </i>toxicity of Sunstones<sup>TM</sup> and dose response curves for Sunstones<sup>TM</sup>-mediated PDT. Human NSCLC cells were incubated with/without Photofrin<sup>TM</sup> (photosensitizer). Experimental groups included: Infrared light treatment (IR), IR+Photofrin<sup>TM</sup>, IR+Sunstones<sup>TM</sup>, and IR+Sunstones<sup>TM</sup>+Photofrin<sup>TM</sup>. Groups were exposed to 2.5W of 808nm light and assayed for metabolic activity. Results: In vitro toxicity assays showed no significant toxicological side effects after 1 week incubation with Sunstones<sup>TM</sup> and demonstrated linear response in cytotoxicity as treatment times and infrared dose increased. IR+Sunstones<sup>TM</sup>+Photofri<sup>TM</sup> group showed significantly decreased metabolic activity compared to control cells, cells treated with IR+Sunstones<sup>TM</sup>, and IR alone. Conclusion: Sunstones<sup>TM</sup> are nontoxic nanocrystals capable of activating photosensitizers for PDT. Future directions include conjugation of up-converters to a novel photosensitizer and managing the selective uptake of conjugate by tumor cells.
Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency (2010)

For the promise of human induced pluripotent stem cells (iPSCs) to be realized, it is necessary to ask if and how efficiently they may be differentiated to functional cells of various lineages. Here, we have directly compared the neural-differentiation capacity of human iPSCs and embryonic stem cells (ESCs). We have shown that human iPSCs use the same transcriptional network to generate neuroepithelia and functionally appropriate neuronal types over the same developmental time course as hESCs in response to the same set of morphogens; however, they do it with significantly reduced efficiency and increased variability. These results were consistent across iPSC lines and independent of the set of reprogramming transgenes used to derive iPSCs as well as the presence or absence of reprogramming transgenes in iPSCs. These findings, which show a need for improving differentiation potency of iPSCs, suggest the possibility of employing human iPSCs in pathological studies, therapeutic screening, and autologous cell transplantation.
High‐Level Resistance of Cytomegalovirus to Ganciclovir Is Associated with Alterations in Both the UL97 and DNA Polymerase Genes (1997)

Mutations in both the viral phosphotransferase gene, UL97, and the DNA polymerase gene, UL54, have been shown to confer ganciclovir resistance to cytomegalovirus (CMV). Moreover, UL54 alterations have been associated with in vitro cross-resistance of CMV to cidofovir. To investigate the relative significance of UL97 versus UL54 alterations in conferring antiviral resistance, phenotypic and genotypic characterization of 28 ganciclovir-resistant clinical CMV isolates was undertaken. Isolates were either low-level ganciclovir-resistant, which have ganciclovir ID50 values > or =8 microM and <30 microM and sensitivity to cidofovir, or high-level ganciclovir-resistant, which have ganciclovir ID50 values > or =30 microM and cross-resistance to cidofovir. Low-level ganciclovir-resistant isolates were associated with UL97 alterations and short periods of ganciclovir treatment, while high-level ganciclovir-resistant isolates were associated with both UL97 and polymerase alterations and were cultured after extended ganciclovir therapy.
The very low‐pressure pyrolysis of phenyl ethyl ether, phenyl allyl ether, and benzyl methyl ether and the enthalpy of formation of the phenoxy radical (1977)

Abstract A value of the enthalpy of formation of the phenoxy radical in the gas phase, Δ H ° ,298K (ϕO·, g) = 11.4 ± 2.0 kcal/mol, has been obtained from the kinetic study of the unimolecular decompositions of phenyl ethyl ether, phenyl allyl ether, and benzyl methyl ether Trivial names for ethoxy benzene, 2‐propenoxy (allyloxy) benzene, and α‐methoxytoluene, respectively at very low pressures. Bond fission, producing phenoxy or benzyl radicals, respectively, is the only mode of decomposition in each case. The present value leads to a bond dissociation energy BDE(ϕO—H) = 86.5 ± 2 kcal/mol, 1 kcal = 4.18674 kJ (absolute) in good agreement with recent estimates made on the basis of competitive oxidation steps in the liquid phase. A comparison with bond dissociation energies of aliphatic alcohols, BDE(RO—H) = 104 kcal/mol, reveals that the stabilization energy of the phenoxy radical (17.5 kcal/mol) is considerably greater than the one observed for the isoelectronic benzyl radical (13.2 kcal/mol). Decomposition of phenoxy radicals into cyclopentadienyl radicals and CO has been observed at temperatures above 1000°K, and a mechanism for this reaction is proposed.
Morphology and growth of extended chain crystals of polyethylene (1968)

Abstract The morphology and growth of extended chain crystals of polyethylene is discussed on the basis of optical and electron microscopy. The spherulitic habit is shown to be caused by nucleation of new lamellae on the (001) surface of lamellae, branching of lamellae on their growth face, and thickening of lamellae. Spherulite centers have been identified down to the primary lamella. Analysis of intersections of lamellae during crystallization allowed the identification of intermediate stages of crystal growth. Fracture surfaces parallel to the growth face and the (001) face are discussed. “Ripple decoration” by surface recrystallization is developed as a tool for fracture surface study. Kink bands are described as growth defects. Bending of lamellae is shown to go by slip parallel to the polymer chains. Ripple and drawn out fiber annealing is analyzed. All observations on extended chain crystals are used to propose a mechanism of extended chain crystal growth of polyethylene under elevated pressur.
Investigation of 600 V GaN HEMTs for high efficiency and high temperature applications (2014)

This paper investigates the fast switching characteristics and high temperature performance of the emerging 600 V GaN high-electron-mobility transistor (HEMT) for high efficiency / high temperature applications. First, the inherent switching performance of the GaN HEMT is demonstrated in the double pulse test. The GaN HEMT exhibits superior switching capability, with a di/dt reaching 9.6 A/ns and dv/dt reaching 140 V/ns. Then, the limitations of the fast switching capability by the device packaging and application circuit are analyzed. The interference between the current and gate through common source inductance limits the inherent switching speed. Packaging and circuit layout with small parasitics is critical in achieving fast switching. Finally, the high temperature static and switching characteristics up to 200 °C are also tested and given. The switching performance of the device is temperature insensitive.
Form birefringence dispersion in periodic layered media (1996)

We analyze the form birefringence dispersion of periodic dielectric layered media. Using Bloch wave analysis, we investigate the shape of the normal surface and its dependence on wavelength. Our higher-order uniaxial approximation gives an explicit expression for the additional dispersion of the form birefringence that is due to the finite layer thickness.
Primate-specific Melanoma Antigen-A11 Regulates Isoform-specific Human Progesterone Receptor-B Transactivation (2012)

Progesterone acting through the progesterone receptor (PR) and its coregulators prepares the human endometrium for receptivity to embryo implantation and maintains pregnancy. The menstrual cycle-dependent expression of melanoma antigen-A11 (MAGE-11) in the mid-secretory human endometrium suggested a novel function in human PR signaling. Here we show that MAGE-11 is an isoform-specific coregulator responsible for the greater transcriptional activity of human PR-B relative to PR-A. PR was recruited to progesterone response regions of progesterone-regulated FK506-binding protein 5 (FKBP5) immunophilin and small Ras family G protein cell growth inhibitor RASD1 genes. Expression of MAGE-11 lentivirus shRNA in human endometrial Ishikawa cells expressing PR-B showed that MAGE-11 is required for isoform-specific PR-B up-regulation of FKBP5. In contrast, MAGE-11 was not required for progesterone up-regulation of RASD1 in endometrial cells expressing the PR-A/B heterodimer. Target gene specificity of PR-B depended on the synergistic actions of MAGE-11 and p300 mediated by the unique PR-B NH(2)-terminal (110)LLXXVLXXLL(119) motif that interacts with the MAGE-11 F-box region in a phosphorylation- and ubiquitinylation-dependent manner. A progesterone-dependent mechanism is proposed in which MAGE-11 and p300 increase PR-B up-regulation of the FKBP5 gene. MAGE-11 down-regulates PR-B, similar to the effects of progesterone, and interacts with FKBP5 to stabilize a complex with PR-B. We conclude that the coregulator function of MAGE-11 extends to isoform-specific regulation of PR-B during the cyclic development of the human endometrium.
Tetramolecular immune complexes are more efficient than IVIg to prevent antibody‐dependent in vitro and in vivo phagocytosis of blood cells (2004)

Intravenous immunoglobulins (IVIg) have immunomodulatory effects in vivo and are widely used in the treatment of autoimmune diseases, such as idiopathic thrombocytopenic purpura (ITP). The mechanisms by which IVIg can prevent platelet clearance in ITP patients are not fully understood but are known to require the participation of low affinity Fcgamma receptors (FcgammaRs), which interact poorly with monomeric immunoglobulin G (IgG). Given the importance of low affinity FcgammaRs in the treatment of ITP, we hypothesized that immune complexes (IC) produced in vitro could reproduce the effects of IVIg. Small-size tetramolecular IC were prepared using mouse monoclonal anti-human IgG and human Fc fragments. The effects of tetramolecular IC and IVIg on the in vitro and in vivo inhibition of phagocytosis of opsonized blood cells were compared. The results obtained showed that tetramolecular IC were at least six times more efficient than IVIg to prevent phagocytosis of opsonized red blood cells in vitro, and clearance of platelets in the thrombocytopenic mouse model.
Characterization of N-terminal processing of group VIA phospholipase A2 and of potential cleavage sites of amyloid precursor protein constructs by automated identification of signature peptides in LC/MS/MS analyses of proteolytic digests (2004)

Dysregulation of proteolytic processing of the amyloid precursor protein (APP) contributes to the pathogenesis of Alzheimer's Disease, and the Group VIA phospholipase A(2) (iPLA(2)beta) is the dominant PLA(2) enzyme in the central nervous system and is subject to regulatory proteolytic processing. We have identified novel N-terminal variants of iPLA(2)beta and previously unrecognized proteolysis sites in APP constructs with a C-terminal 6-myc tag by automated identification of signature peptides in LC/MS/MS analyses of proteolytic digests. We have developed a Signature-Discovery (SD) program to characterize protein isoforms by identifying signature peptides that arise from proteolytic processing in vivo. This program analyzes MS/MS data from LC analyses of proteolytic digests of protein mixtures that can include incompletely resolved components in biological samples. This reduces requirements for purification and thereby minimizes artifactual modifications during sample processing. A new algorithm to generate the theoretical signature peptide set and to calculate similarity scores between predicted and observed mass spectra has been tested and optimized with model proteins. The program has been applied to the identification of variants of proteins of biological interest, including APP cleavage products and iPLA(2)beta, and such applications demonstrate the utility of this approach.