gebhart/patrepeval huggingface dataset:
Purification, Molecular Cloning, and Characterization of TRP32, a Novel Thioredoxin-related Mammalian Protein of 32 kDa (1998)

We purified a protein of 32 kDa from human thymoma HPB-ALL cells that was co-purified with a catalytic fragment of MST (mammalian STE-20-like), a kinase of the STE20 family, which is proteolytically activated by caspase in apoptosis (Lee, K.-K., Murakawa, M., Nishida, E., Tsubuki, S., Kawashima, S., Sakamaki, K., and Yonehara, S. (1998) Oncogene 16, in press). Molecular cloning of the gene encoding this 32-kDa protein (TRP32) reveals that it is a novel protein of 289 amino acid residues and contains an NH2-terminal thioredoxin domain with a conserved thioredoxin active site. The human and mouse TRP32 proteins have 99% homology, and the thioredoxin domains are completely identical. The thioredoxin domain of TRP32 has thioredoxin-like reducing activity, which can reduce the interchain disulfide bridges of insulin in vitro. However, the thioredoxin domain of TRP32 is more sensitive to oxidation than human thioredoxin. Northern blot analysis showed that TRP32 is expressed in all human tissues. Expression of TRP32 was also confirmed in all mammalian cell lines tested by Western blot analysis using anti-TRP32 monoclonal antibody. Subcellular fractionation and immunostaining analysis showed TRP32 is cytoplasmic protein. These findings suggest that TRP32 is a novel cytoplasmic regulator of the redox state in higher eukaryotes.
Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generatedin vitro from CD34+ hematopoietic progenitor cells (2000)

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that can be used for vaccination purposes, to induce a specific T-cell response in vivo against melanoma-associated antigens. We have shown that the sequential use of early-acting hematopoietic growth factors, stem cell factor, IL-3 and IL-6, followed by differentiation with IL-4 and granulocyte-macrophage colony-stimulating factor allows the in vitro generation of large numbers of immature DCs from CD34(+) peripheral blood progenitor cells. Maturation to interdigitating DCs could specifically be induced within 24 hr by addition of TNF-alpha. Here, we report on a phase I clinical vaccination trial in melanoma patients using peptide-pulsed DCs. Fourteen HLA-A1(+) or HLA-A2(+) patients received at least 4 i.v. infusions of 5 x 10(6) to 5 x 10(7) DCs pulsed with a pool of peptides including either MAGE-1, MAGE-3 (HLA-A1) or Melan-A, gp100, tyrosinase (HLA-A2), depending on the HLA haplotype. A total of 83 vaccinations were performed. Clinical side effects were mild and consisted of low-grade fever (WHO grade I-II). Clinical and immunological responses consisted of anti-tumor responses in 2 patients, increased melanoma peptide-specific delayed-type hypersensitivity reactions in 4 patients, significant expansion of Melan-A- and gp100-specific cytotoxic T lymphocytes in the peripheral blood lymphocytes of 1 patient after vaccination and development of vitiligo in another HLA-A2(+) patient. Our data indicate that the vaccination of peptide-pulsed DCs is capable of inducing clinical and systemic tumor-specific immune responses without provoking major side effects.
Polymer LEDSs (1992)

Traditionally, polymers have been known for their flexibility and ease of processing, but not for their electrical properties. Then it was found that polymers could be grown in such a way that they demonstrated semi-conducting properties. This arises from overlap of electron orbitals along the polymer chain, forming a valence and a conduction band, analogous to how these form in silicon. Such materials, termed "conjugated" polymers, are extremely attractive in that they combine semiconductor properties with the advantages of processing and the mechanical properties associated with polymers. Thin-film structures can be fabricated from these polymers, including semiconductor devices such as field-effect transistors which can be prepared over large areas. Recently we have found that conjugated polymers, with improved purity, and which show very strong photoluminescence, can form the "active" or electroluminescent layer in light-emitting diodes (LEDs). Materials processing and device growing has now reached a stage where control of the colour of light emitted and levels of efficiency are acceptable for display applications, such as instrument panels and pixellated flat-screen displays.
Ca(2+)-independent reduction of N-methyl-D-aspartate channel activity by protein tyrosine phosphatase. (1996)

Regulation of ion channel function by intracellular processes is fundamental for controlling synaptic signaling and integration in the nervous system. Currents mediated by N-methyl-D-aspartate (NMDA) receptors decline during whole-cell recordings and this may be prevented by ATP. We show here that phosphorylation is necessary to maintain NMDA currents and that the decline is not dependent upon Ca2+. A protein tyrosine phosphatase or a peptide inhibitor of protein tyrosine kinase applied intracellularly caused a decrease in NMDA currents even when ATP was included. On the other hand, pretreating the neurons with a membrane-permeant tyrosine kinase inhibitor occluded the decline in NMDA currents when ATP was omitted. In inside-out patches, applying a protein tyrosine phosphatase to the cytoplasmic face of the patch caused a decrease in probability of opening of NMDA channels. Conversely, open probability was increased by a protein tyrosine phosphatase inhibitor. These results indicate that NMDA channel activity is reduced by a protein tyrosine phosphatase associated with the channel complex.
Advances in PEGylation of important biotech molecules: delivery aspects (2008)

This review will discuss recent achievements in PEGylation processes with an emphasis on novel PEG-drugs constructs, the unrealized potential of PEGylation for non-injected routes of delivery, and also on PEGylated versions of polymeric nanoparticles, including dendrimers and liposomes.
Effect of Cervical Spine Motion on the Neuroforaminal Dimensions of Human Cervical Spine (1992)

A nerve root impingement within a stenotic neuroforamen is a common sequela of cervical degenerative arthritis and herniated nucleus pulposus. Understanding of the effects of cervical position on foraminal size is important in the assessment of pathology and injury, for selection of a provocative maneuver to elicit symptoms and in selecting a position of immobilization for the management of nerve root impingement syndrome. This biomechanical study of human cadaver cervical spines reports the measured variations in the sizes of neuroforamina as a function of cervical positioning. Five fresh frozen adult human cadaver cervical spines (C2-T1) were tested with combinations of flexion-extension and rotational position. Ten pounds of axial load was applied to simulate a normal loading of a cervical spine. The foramina of C5, C6, and C7 were directly measured using a set of finely graded circular probes. Compared to the foraminal diameter at the neutral position, there were statistically significant reductions in the foramen diameter of 10% and 13%, at 20 degrees and 30 degrees of extension respectively (P < 0.01). Conversely, in flexion, there were statistically significant increase of 8% and 10% at 20 degrees and 30 degrees of flexion respectively (P < 0.01). Though there was a reduction in the foraminal size with ipsilateral 20 degrees rotation, and an increase with contralateral 20 degrees rotation, these changes were not significantly different from the mean of the control. Combinations of flexion or extension position with axial rotation did not significantly change the foraminal size compared to the respective sagittal position with no axial rotation.(ABSTRACT TRUNCATED AT 250 WORDS)
Is inflammation the cause of pre-eclampsia? (2011)

It has been proposed that either excessive inflammation or an imbalance in angiogenic factors cause pre-eclampsia. In the present review, the arguments for and against the role of inflammation and/or angiogenic imbalance as the cause of pre-eclampsia are discussed on the basis of the Bradford-Hill criteria for disease causation. Although both angiogenic imbalance and systemic inflammation are implicated in pre-eclampsia, the absence of temporality of inflammatory markers with pre-eclampsia challenges the concept that excessive inflammation is the cause of pre-eclampsia. In contrast, the elevation of anti-angiogenic factors that precede the clinical signs of pre-eclampsia fulfils the criterion of temporality. The second most important criterion is the dose-response relationship. Although such a relationship has not been proven between pro-inflammatory cytokines and pre-eclampsia, high levels of anti-angiogenic factors have been shown to correlate with increased incidence and disease severity, hence satisfying this condition. Finally, as the removal of circulating sFlt-1 (soluble Fms-like tyrosine kinase receptor-1) from pre-eclamptic patients significantly improves the clinical outcome, it fulfils the Hill's experiment principle, which states that removal of the cause by an appropriate experimental regimen should ameliorate the condition. In contrast, treatment with high doses of corticosteroid fails to improve maternal outcome in pre-eclampsia, despite suppressing inflammation. Inflammation may enhance the pathology induced by the imbalance in the angiogenic factors, but does not by itself cause pre-eclampsia. Development of therapies based on the angiogenic and cytoprotective mechanisms seems more promising.
Sapphire ball lens-based fiber probe for common-path optical coherence tomography and its applications in corneal and retinal imaging (2012)

We describe a common-path swept source optical coherence tomography fiber probe design using a sapphire ball lens for cross-sectional imaging and sensing for retina vitrectomy surgery. The high refractive index (n=1.75) of the sapphire ball lens improves the focusing power and enables the probe to operate in the intraocular space. The highly precise spherical shape of the sapphire lens also reduces astigmatism and coma compared to fused nonspherical ball lenses. A theoretical sensitivity model for common-path optical coherence tomography (CP-OCT) was developed to assess its optimal performance based on an unbalanced photodetector configuration. Two probe designs-with working distances 415 and 1221 μm and lateral resolution 11 and 18 μm-were implemented with sensitivity up to 88 dB, which is significantly higher than previously reported CP-OCT probes. We assessed the performances of the fiber probes by cross-sectional imaging a bovine cornea and retina in air and in vitreous gel with a 1310 nm swept source OCT system. To the best of our knowledge, this is the first demonstration of sapphire ball lens-based CP-OCT probes directly inserted into the vitreous gel of a bovine eyeball for ocular imaging with a sensitivity approaching the theoretical limitation of CP-OCT.
Lead Salt Quantum Dots:  the Limit of Strong Quantum Confinement (2000)

Nanocrystals or quantum dots of the IV-VI semiconductors PbS, PbSe, and PbTe provide unique properties for investigating the effects of strong confinement on electrons and phonons. The degree of confinement of charge carriers can be many times stronger than in most II-VI and III-V semiconductors, and lead salt nanostructures may be the only materials in which the electronic energies are determined primarily by quantum confinement. This Account briefly reviews recent research on lead salt quantum dots.
Tumor-Stromal Interactions Influence Radiation Sensitivity in Epithelial- versus Mesenchymal-Like Prostate Cancer Cells (2010)

HS-27a human bone stromal cells, in 2D or 3D coultures, induced cellular plasticity in human prostate cancer ARCaP(E) and ARCaP(M) cells in an EMT model. Cocultured ARCaP(E) or ARCaP(M) cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaP(E) exhibiting the most significant increases in presence of bone or prostate stroma cells. Prostate (Pt-N or Pt-C) or bone (HS-27a) stromal cells induced significant resistance to radiation treatment in ARCaP(E) cells compared to ARCaP(M) cells. However pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin blocking antibody (CNT095) significantly decreased stromal cell-induced radiation resistance in both ARCaP(E)- and ARCaP(M)-cocultured cells. Taken together the data suggest that mesenchymal-like cancer cells reverting to epithelial-like cells in the bone microenvironment through interaction with bone marrow stromal cells and reexpress E-cadherin. These cell adhesion molecules such as E-cadherin and integrin alpha v in cancer cells induce cell survival signals and mediate resistance to cancer treatments such as radiation.
Major Degradation Product Identified in Several Pharmaceutical Formulations against the Common Cold (2006)

Different pharmaceutical preparations against the common cold contain acetaminophen, phenylephrine hydrochloride, and chlorpheniramine maleate. A degradation product had been discovered in these preparations after short- and long-term stability studies. This degradation product was isolated and found to be an adduct of phenylephrine and maleic acid. An account of the isolation and characterization of this compound was published. Our interest in this area led us to synthesize the compound, and we found that the synthesized compound does not have the same spectroscopic properties described in the original paper. Our subsequent work identified the structure of the degradation product as a "Michael addition" product of phenylephrine and maleic acid.
Targeted Activation of Toll-Like Receptors: Conjugation of a Toll-Like Receptor 7 Agonist to a Monoclonal Antibody Maintains Antigen Binding and Specificity (2015)

Therapeutic activation of Toll-like receptors (TLR) has potential for cancer immunotherapy, for augmenting the activity of antitumor monoclonal antibodies (mAbs), and for improved vaccine adjuvants. A previous attempt to specifically target TLR agonists to dendritic cells (DC) using mAbs failed because conjugation led to nonspecific binding and mAbs lost specificity. We demonstrate here for the first time the successful conjugation of a small molecule TLR7 agonist to an antitumor mAb (the anti-hCD20 rituximab) without compromising antigen specificity. The TLR7 agonist UC-1V150 was conjugated to rituximab using two conjugation methods, and yield, molecular substitution ratio, retention of TLR7 activity, and specificity of antigen binding were compared. Both conjugation methods produced rituximab-UC-1V150 conjugates with UC-1V150: rituximab ratio ranging from 1:1 to 3:1 with drug loading quantified by UV spectroscopy and drug substitution ratio verified by MALDI TOF mass spectroscopy. The yield of purified conjugates varied with conjugation method and dropped as low as 31% using a method previously described for conjugating UC-1V150 to proteins, where a bifunctional cross-linker was first reacted with rituximab and second to the TLR7 agonist. We therefore developed a direct conjugation method by producing an amine-reactive UV active version of UC-1V150, termed NHS:UC-1V150. Direct conjugation with NHS:UC-1V150 was quick and simple and gave improved conjugate yields of 65-78%. Rituximab-UC-1V150 conjugates had the expected pro-inflammatory activity in vitro (EC50 28-53 nM) with a significantly increased activity over unconjugated UC-1V150 (EC50 547 nM). Antigen binding and specificity of the rituxuimab-UC-1V150 conjugates was retained, and after incubation with human peripheral blood leukocytes, all conjugates bound strongly only to CD20-expressing B cells while no nonspecific binding to CD20-negative cells was observed. Selective targeting of Toll-like receptor activation directly within tumors or to DC is now feasible.
Mitochondrial production of reactive oxygen species contributes to the β‐adrenergic stimulation of mouse cardiomycytes (2011)

The sympathetic adrenergic system plays a central role in stress signalling and stress is often associated with increased production of reactive oxygen species (ROS). Furthermore, the sympathetic adrenergic system is intimately involved in the regulation of cardiomyocyte Ca2+ handling and contractility. In this study we hypothesize that endogenously produced ROS contribute to the inotropic mechanism of β-adrenergic stimulation in mouse cardiomyocytes. Cytoplasmic Ca2+ transients, cell shortening and ROS production were measured in freshly isolated cardiomyocytes using confocal microscopy and fluorescent indicators. As a marker of oxidative stress, malondialdehyde (MDA) modification of proteins was detected with Western blotting. Isoproterenol (ISO), a β-adrenergic agonist, increased mitochondrial ROS production in cardiomyocytes in a concentration- and cAMP–protein kinase A-dependent but Ca2+-independent manner. Hearts perfused with ISO showed a twofold increase in MDA protein adducts relative to control. ISO increased Ca2+ transient amplitude, contraction and L-type Ca2+ current densities (measured with whole-cell patch-clamp) in cardiomyocytes and these increases were diminished by application of the general antioxidant N-acetylcysteine (NAC) or the mitochondria-targeted antioxidant SS31. In conclusion, increased mitochondrial ROS production plays an integral role in the acute inotropic response of cardiomyocytes to β-adrenergic stimulation. On the other hand, chronically sustained adrenergic stress is associated with the development of heart failure and cardiac arrhythmias and prolonged increases in ROS may contribute to these defects.
Manipulation of the Alternative NF‐κB Pathway in Mice Has Sexually Dimorphic Effects on Bone (2018)

Alternative NF-κB signaling promotes osteoclastogenesis and pathological bone loss, but the effect of sex on phenotype has not been explored. We disrupted alternative NF-κB signaling by deletion of upstream kinase NF-κB-inducing kinase (NIK) or NF-κB subunit RelB and found that both NIK-deficient and RelB-deficient female mice possessed more than twofold higher trabecular bone mass compared to controls, whereas no differences were observed in males. In vitro, RelB-deficient precursors from female mice showed a more severe osteoclast (OC) differentiation defect than male, while WT had no sex bias. Next, we asked whether pharmacologic activation of alternative NF-κB by inhibitor of apoptosis (IAP) antagonist BV6 has sex-dependent effects on bone. Unlike male mice that lost bone, female mice on BV6 for 4 weeks showed no changes in either trabecular bone mass or OC number. Because estrogen generally suppresses NF-κB, we hypothesized that estrogen protects bone from BV6 effects in vivo. Thus, we performed ovariectomy or sham surgery in female mice, then treated with BV6 or vehicle for 4 weeks. Although ovariectomy caused bone loss, BV6 did not have any additional impact, suggesting that direct estrogen effects do not cause resistance to BV6 in vivo. The osteopenic effects of IAP antagonists in males may have implications for their use in cancer therapy. © 2018 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Diameter dependence of the RamanD-band in isolated single-wall carbon nanotubes (2001)

Raman D-band spectra are reported for several different SWNTs using two different laser energies ${(E}_{\mathrm{laser}}=1.58$ and 2.41 eV). At a fixed ${E}_{\mathrm{laser}},$ individual isolated SWNTs exhibit different diameter-dependent D-band frequencies ${\ensuremath{\omega}}_{D}$ around an average value. For both semiconducting and metallic tubes, ${\ensuremath{\omega}}_{D}$ decreases with decreasing nanotube diameter, though ${\ensuremath{\omega}}_{D}$ for isolated metallic SWNTs is higher than for isolated semiconducting SWNTs. The average D-band frequency depends linearly on ${E}_{\mathrm{laser}},$ as previously observed for SWNT bundles, suggesting that the D-band in SWNTs is activated by defects or by the finite size of the SWNTs.
Survival and recovery of human platelets stored for five days in a non- plasma medium (1986)

Human blood platelets were stored for five days as concentrates in 60 mL of: (a) plasma; (b) non-plasma medium with anticoagulant; and (c) non-plasma medium without anticoagulant. All preparations were equally functional when tested for platelet aggregation and release reaction in response to single agonist or synergistic pairs of agonists in vitro. Platelets stored in non-plasma medium with anti-coagulant had lower kallikrein, fibrino(gen)peptide A, lactate, and beta-thromboglobulin than did plasma controls after five days. In vivo recovery and survival of platelets stored in non-plasma medium with anticoagulant were 51.2% +/- 4.3% and 8.7 +/- 0.3 days, respectively, which were not statistically different from plasma controls of 39.2% +/- 4.9% and 7.2 +/- 0.8 days, respectively. It is concluded that platelets can be stored for five days in a non-plasma medium and still have good in vivo recoveries and survivals.
Inferring causal genomic alterations in breast cancer using gene expression data (2011)

To our knowledge, this is the first effort to systematically identify and validate drivers for expression based CNV regions in breast cancer. The framework where the wavelet analysis of copy number alteration based on expression coupled with the gene regulatory network analysis, provides a blueprint for leveraging genomic data to identify key regulatory components and gene targets. This integrative approach can be applied to many other large-scale gene expression studies and other novel types of cancer data such as next-generation sequencing based expression (RNA-Seq) as well as CNV data.
Soluble Complement Receptor-1 Protects Heart, Lung, and Cardiac Myofilament Function From Cardiopulmonary Bypass Damage (2000)

sCR1 meaningfully moderates the post-CPB syndrome, supporting the hypothesis that complement activation contributes to this syndrome.
Testosterone allosterically regulates ethanol oxidation by homo- and heterodimeric gamma-subunit-containing isozymes of human alcohol dehydrogenase. (1986)

Testosterone and its physiologically active metabolite 5 alpha-dihydrotestosterone are selective, allosteric inhibitors of the gamma subunit-containing isozymes of class I human alcohol dehydrogenase (ADH) with apparent Ki values for testosterone at pH 7.4 between 3.5 and 16 X 10(-6) M. Testosterone inhibition is noncompetitive with respect to ethanol, NAD+, 1,10-phenanthroline, and 4-methylpyrazole, identifying a regulatory site distinct from the catalytic site. Testosterone does not inhibit the class I isozymes composed only of alpha and/or beta subunits and only weakly inhibits the class II and III isozymes. Importantly, none of these human ADH isozymes oxidize or reduce the steroids with the delta 4 double bond or 5 alpha configuration. The allosteric effect of testosterone, restricted to the gamma subunits of human ADH, suggests unique metabolic specificities and pathways for these isozymes, apart from all others. This inhibition may ultimately be critical to an identification of their function(s). Analogous considerations of other metabolic effectors might further lead to similar insights regarding the alpha and beta subunit-containing isozymes as well as the class II and III ADH.