gebhart/patrepeval huggingface dataset:
Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1–targeted therapy in lung cancer patients (2017)

Exhausted T cells in chronic infections and cancer have sustained expression of the inhibitory receptor programmed cell death 1 (PD-1). Therapies that block the PD-1 pathway have shown promising clinical results in a significant number of advanced-stage cancer patients. Nonetheless, a better understanding of the immunological responses induced by PD-1 blockade in cancer patients is lacking. Identification of predictive biomarkers is a priority in the field, but whether peripheral blood analysis can provide biomarkers to monitor or predict patients' responses to treatment remains to be resolved. In this study, we analyzed longitudinal blood samples from advanced stage non-small cell lung cancer (NSCLC) patients (<i>n</i> = 29) receiving PD-1-targeted therapies. We detected an increase in Ki-67+ PD-1+ CD8 T cells following therapy in ∼70% of patients, and most responses were induced after the first or second treatment cycle. This T-cell activation was not indiscriminate because we observed only minimal effects on EBV-specific CD8 T cells, suggesting that responding cells may be tumor specific. These proliferating CD8 T cells had an effector-like phenotype (HLA-DR<sup>+</sup>, CD38<sup>+</sup>, Bcl-2<sup>lo</sup>), expressed costimulatory molecules (CD28, CD27, ICOS), and had high levels of PD-1 and coexpression of CTLA-4. We found that 70% of patients with disease progression had either a delayed or absent PD-1+ CD8 T-cell response, whereas 80% of patients with clinical benefit exhibited PD-1+ CD8 T-cell responses within 4 wk of treatment initiation. Our results suggest that peripheral blood analysis may provide valuable insights into NSCLC patients' responses to PD-1-targeted therapies.
A fast, robust pattern recognition asystem for low light level image registration and its application to retinal imaging (1997)

We describe an image processing system which we have developed to align autofluorescence and high-magnification images taken with a laser scanning ophthalmoscope. The low signal to noise ratio of these images makes pattern recognition a non-trivial task. However, once n images are aligned and averaged, the noise levels drop by a factor of n and the image quality is improved. We include examples of autofluorescence images and images of the cone photoreceptor mosaic obtained using this system.
High plasma tumor necrosis factor (TNF)-alpha concentrations and a sepsis-like syndrome in patients undergoing hyperthermic isolated limb perfusion with recombinant TNF-alpha, interferon-gamma, and melphalan (1996)

Hyperthermic isolated limb perfusion with recombinant TNF-alpha leads to high systemic concentrations of TNF-alpha, probably due to leakage of recombinant TNF-alpha from the perfusion circuit, mainly through collateral blood flow. A sepsis-like syndrome is seen in all patients. Despite high concentrations of systemic TNF-alpha, this sepsis syndrome is short-lived and recovery is rapid and complete in most patients.
Cancer immunotherapy of established tumors with IL-12. Effective delivery by genetically engineered fibroblasts (1995)

IL-12 is a heterodimeric cytokine produced by macrophages, mitogen stimulated- or EBV infected-B lymphocytes, keratinocytes, and probably dendritic cells, with important immunoregulatory functions in vitro and in vivo. It directly stimulates activated NK and T cells to produce high levels of IFN-gamma, enhances their cytolytic activity, and promotes maturation of Th1 cells as well as IL-2-activated B cells. We have tested paracrine delivery of IL-12 using autologous or allogeneic fibroblasts engineered to secrete high levels of IL-12 to treat established tumors. Injection of IL-12-engineered fibroblasts at the site of an established (day 8) MCA207 sarcoma could efficiently eliminate or suppress tumor growth in a dose-dependent manner, requiring delivery of > 150 ng/kg/dose of bioactive IL-12. Weekly inoculations for 3 wk could also be used to effectively treat a day 4 sarcoma located intradermally in the opposite flank (80% protection using autologous fibroblasts), resulting in long-term protective antitumor immunity. In less immunogenic tumors (MCA102, MC38), 7-day established lung metastases could be significantly reduced (p = 0.001) following IL-12 delivery by fibroblasts and systemic administration of low doses of IL-2. Histologic findings included a mixed infiltrate of CD4+ and CD8+ T effectors and macrophages in the regressing sarcoma on day 21. In a day 41 MCA207 sarcoma locally injected in situ, similar findings were observed. No lymphoid hyperplasia or tissue necrosis were noted in liver, spleen, or lungs in mice receiving repeated inocula of IL-12-engineered fibroblasts. Tests of liver and renal function monitored during the repetitive weekly treatments were within the normal range. IL-12-engineered fibroblasts thus seem to serve as a safe and efficient means to deliver IL-12 in these three tumor models.
Microscopic Protonation Mechanism of Branched Polyamines: Poly(amidoamine) versus Poly(propyleneimine) Dendrimers (2007)

The protonation mechanisms of the poly(amidoamine) (PAMAM) andpoly(propyleneimine) (PPI) dendrimers are clarified and related to their molecular structure. The overall proton binding isotherms can be interpreted in terms of a site binding model, which involves a limited number of parameters, and can be used to gain detailed insight in both macroscopic and microscopic protonation mechanisms. The protonation of the PAMAM dendrimers is dominated by the chemical environment of the amine sites, and the sites protonate almost independently leading to protonation mechanism with a characteristic intermediate core-shell structure. In the case of PPI, the protonation is dominated by the electrostatic nearest-neighbor repulsions between the protonated sites, and leads to an intermediate »onion-like« structure where all the odd shells are protonated. Copyright of Croatica Chemica Acta is the property of Croatian Chemical Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.
Purification and characterization of furostanol glycoside 26‐O‐β‐glucosidase from Costus speciosus rhizomes (1996)

In plants, spirostanol glycosides (steroid saponins) are known to be formed furostanol glycosides during postharvest treatment and storage. Furostanol glycoside 26-O-beta-glucosidase (F26G) involved in this conversion was purified to apparent homogeneity for the first time from Costus speciosus rhizomes which accumulate these glycosides. The enzyme was highly specific for cleavage of the C-26-boudn glucose moiety of furostanol glycosides showing Km for protogracillin of 50 microM. Glucono-1,5-lactone, a typical beta-glucosidase inhibitor, and diosgenin, an aglycone of spirostanol glycosides, strongly inhibited the enzyme activity. The purified F26G is dimeric with a native apparent molecular weight of 110,000 consisting of subunits of 54,000 and 58,000. The N-terminal sequence of the 54,000 protein has a high similarity to the sequences found in N-terminal regions of known plant beta-glucosidases.
Potential Applications of Untethered Microdevices in the Blood Vessels within the Constraints of an MRI System (2005)

This paper presents potential medical applications that an untethered microdevice in the cardiovascular system could perform within an MRI system. Recent developments and continuing evolution in micro/nano fabrication and design techniques will enable the development of functional microdevices able to explore the cardiovascular system. The Magnetic Resonance Submarine (MR-Sub) project is a first step towards this goal. Magnetic force generated by the gradient coils of an MRI system provides a propulsion mechanism that simplifies miniaturization and bypasses energetic challenges. Untethered microdevices may play an important complementary role in the next generation of minimally invasive tools. A better efficiency and targetability of the treatments will be achieved when microsystems such as the MR-Sub will allow a more extensive access to smaller blood vessels.
Homeostasis of Peripheral B Cells in the Absence of B Cell Influx from the Bone Marrow (2001)

To study homeostasis of peripheral B lymphocytes in the absence of B cell influx from the bone marrow, we generated a mouse mutant in which the recombination-activating gene (RAG)-2 can be inducibly deleted. When RAG-2 was deleted at the age of 8-10 wk, splenic naive follicular B cells were gradually lost over a year of observation, with a half-life of approximately 4.5 mo. By contrast, the pool of marginal zone B cells in the spleen and of B-1 cells in the peritoneal cavity were kept at normal level. In lymph nodes, approximately 90% of the B cells were lost within 4 mo, and B cell numbers remained constant thereafter. Mice in which RAG-2 was deleted at birth maintained a small population of activated B cells with an increased proportion of marginal zone B cells. Additionally, an increase of the pool of IgM secreting cells and B-1a cells was observed.
An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes (2019)

Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.).
Modulation of Single-Cell IgG Secretion Frequency and Rates in Human Memory B Cells by CpG DNA, CD40L, IL-21, and Cell Division (2009)

During the recall response by CD27(+) IgG class-switched human memory B cells, total IgG secreted is a function of the following: 1) the number of IgG-secreting cells (IgG-SC), and 2) the secretion rate of each cell. In this study, we report the quantitative ELISPOT method for simultaneous estimation of single-cell IgG secretion rates and secreting cell frequencies in human B cell populations. We found that CD27(+) IgM(-) memory B cells activated with CpG and cytokines had considerable heterogeneity in the IgG secretion rates, with two major secretion rate subpopulations. BCR cross-linking reduced the frequency of cells with high per-cell IgG secretion rates, with a parallel decrease in CD27(high) B cell blasts. Increased cell death may account for the BCR-stimulated reduction in high-rate IgG-SC CD27(high) B cell blasts. In contrast, the addition of IL-21 to CD40L plus IL-4-activated human memory B cells induced a high-rate IgG-SC population in B cells with otherwise low per-cell IgG secretion rates. The profiles of human B cell IgG secretion rates followed the same biphasic distribution and range irrespective of division class. This, along with the presence of non-IgG-producing, dividing B cells in CpG plus cytokine-activated B memory B cell populations, is suggestive of an on/off switch regulating IgG secretion. Finally, these data support a mixture model of IgG secretion in which IgG secreted over time is modulated by the frequency of IgG-SC and the distribution of their IgG secretion rates.
Differential Roles of NMDA Receptor Subtypes in Ischemic Neuronal Cell Death and Ischemic Tolerance (2008)

We found that NR2A- and NR2B-containing NMDA receptor subtypes play differential roles in ischemic neuronal death and ischemic tolerance, suggesting attractive new strategies for the development of drugs for patients with stroke.
<title>Measurement of blood hematocrit by dual-wavelength near-IR photoplethysmography</title> (1992)

Blood hematocrit is routinely determined in the clinic by analysis of blood samples. This paper introduces an non-invasive method for measuring arterial blood hematocrit which, when combined with pulse oximetry, potentially enables simultaneous monitoring of hemoglobin concentration and oxygen saturation. It is based on the same principles underlying pulse oximetry, except two light sources that emit close to isobestic wavelengths of oxy/deoxyhemoglobin in the near-infrared band (800 nm and 1300 nm) are employed. Hematocrjt is related to the ratios of the pulsatile and nonpulsatile components of the diffuse intensity transmitted through a blood-perfused tissue at these wavelengths. To test the feasibility of the method, we developed an in vitro light-scattering model with optical properties similar to those of skin tissue. Measurements were made using semiconductor light sources and detectors. We discuss the experimental results in the context of theoretical predictions that show the effect of variations in the volume fraction of blood and water in tissue. Finally, potential problems concerning calibration in a clinical setting are addressed.
Regioselective oxidative polymerization of 1,5‐dihydroxynaphthalene catalyzed by bilirubin oxidase in a water–organic solvent mixed solution (1993)

Abstract Bilirubin oxidase (EC1.11.1.7) was used to catalyze the oxidative polymerization of 1,5‐dihydroxynaphthalene to its polymer in a mixed solvent composed of dioxane, ethyl acetate, and acetate buffer. In an aqueous solution, the enzymatic oxidative polymerization hardly occurred and resulted in negligible yield mainly due to the poor solubility of 1,5‐dihydroxynaphthalene. In the mixed solvent the conversion proceeded with a yield of ca. 70%. The polymer yield was studied with respect to reaction time and solvent components. Elemental analysis, UV‐visible, fluorescent, and FT‐IR spectroscopic analyses, proton NMR and electrochemical studies, and solubility in various organic solvents revealed that 1,5‐dihydroxynaphthalene is polymerized by the CC coupling. The molecular weight of the polymeric products solubilized with DMF varied from low molecular weight product to high molecular weight polymer. From the chromatographic studies, the organic solvent–insoluble residue was suggested to be highly polymerized material. Based on these findings a possible mechanism for enzymatic polymerization of 1,5‐dihydroxynaphthalene is presented: less stable intermediates produced enzymatically from 1,5‐dihydroxynaphthalene undergo coupling and polymerization to ortho‐1,5‐dihydroxynaphthalene polymer, thereby resulting in a regioselective polymerization of 1,5‐dihydroxynaphthalene. © 1993 John Wiley &amp; Sons, Inc.
Quantitative analysis of regions of adenovirus E1A products involved in interactions with cellular proteins (1992)

Human adenovirus E1A proteins and oncogene products of several other DNA tumour viruses derive much of their oncogenic potential from interactions with cellular polypeptides. E1A proteins form complexes with p105Rb and a related p107 polypeptide, and with at least three other proteins (p60cycA, p130, and p300); all may be required for cell transformation. Using a series of E1A deletion mutants, we have carried out a quantitative analysis of the binding patterns of cellular proteins to E1A products. Binding of most of the proteins was affected at least partially by mutations within the amino terminal 25 residues, amino acids 36-69 within conserved region 1 (CR1), and residues 121-138 in conserved region 2 (CR2). However, the specific binding characteristics of each protein varied considerably. p300 was the only species for which binding was totally eliminated by deletions at the amino terminus. Removal of regions within CR1 eliminated binding of all species except p107 and p60cycA. Deletion of portions of CR2 reduced or eliminated binding of all proteins except p300. Thus, whereas cellular polypeptides generally were found to interact with the same three regions of E1A proteins, specific interactions varied considerably.
Visualization of Antigen Presentation by Actin-Mediated Targeting of Glycolipid-Enriched Membrane Domains to the Immune Synapse of B Cell APCs (2004)

Glycolipid-enriched membrane (GEM) domains, or lipid rafts, function in signaling in immune cells, but their properties during Ag presentation are less clear. To address this question, GEM domains were studied using fluorescence cell imaging of mouse CH27 B cells presenting Ag to D10 T cells. Our experiments showed that APCs were enriched with GEM domains in the immune synapse, and this occurred in an actin-dependent manner. This enrichment was specific to GEM domains, because a marker for non-GEM regions of the membrane was excluded from the immune synapse. Furthermore, fluorescence photobleaching experiments showed that protein in the immune synapse was dynamic and rapidly exchanged with that in other compartments of CH27 cells. To identify the signals for targeting GEM domains to the immune synapse in APCs, capping of the domains was measured in cells after cross-linking surface molecules. This showed that co-cross-linking CD48 with MHC class II was required for efficient capping and intracellular signaling. Capping of GEM domains by co-cross-linking CD48 and MHC class II occurred with co-capping of filamentous actin, and both domain capping and T cell-CH27 cell conjugation were inhibited by pretreating CH27 cells with latrunculin B. Furthermore, disruption of the actin cytoskeleton of the CH27 cells also inhibited formation of a mature immune synapse in those T cells that did conjugate to APCs. Thus, Ag presentation and efficient T cell stimulation occur by an actin-dependent targeting of GEM domains in the APC to the site of T cell engagement.
Thrombopoietin: a potential T-helper lymphocyte stimulator. Change in T-lymphocyte composition and blood cytokine levels in thrombopoietin cDNA transferred mice. (1998)

The aim of this study was to evaluate the effect of thrombopoietin (TPO) on T lymphocyte in Balb/c mice delivered hTPO cDNA with plasmid vector. Both mature and immature T lymphocytes in central organs increased, but only the CD4+ subset was preferably proliferated in circulation. High serum IFN-gamma was coinciding with the declination of platelet counts, but TNF-alpha was positively associated with the platelet count, while high IL-2 level was similar to the course of TPO expression. Our data suggested that TPO is a stimulator for T lymphocytes, especially the CD4+ subset.
An Algorithm for Automatic Indexing of Oscillation Images using Fourier Analysis (1997)

A fast and reliable algorithm has been developed for auto-indexing oscillation images. The observed reflection positions are used to compute the corresponding reciprocal-lattice vectors assuming a stationary crystal. These vectors are then projected onto a chosen direction. The projections are subjected to a one-dimensional Fourier analysis. A large Fourier term will be found that has a periodicity corresponding to the interplanar distance if the chosen direction happens to be perpendicular to a set of widely separated reciprocal-lattice planes. Exploration of such directions over a hemisphere establishes the best potential basis vectors of the real cell. The program has successfully determined the lengths and directions of basis vectors for numerous unit cells having cell dimensions ranging from 16 to 668 Å and oscillation ranges from 0.2 to 2.0°.
Directionality of sputtered Cu atoms in a hollow cathode enhanced planar magnetron (1993)

Angular distributions of sputtered Cu atoms in a planar magnetron discharge have been measured using a directional quartz microbalance. The discharge, in both Ar and Kr gases, was enhanced at low pressures, e.g., 0.07 Pa, using a hollow cathode electron source. Several means of improving the directionality, i.e., decreasing the angular spread of the sputtered atoms, were investigated. Increasing the discharge voltage to 770 V and increasing the gas pressure to not more than 1 Pa (for a throw distance of 50 mm) marginally improved the directionality of the angular distribution. Significant directionality was achieved using filter collimators which consisted of an array of collimating tubes. Our measurements show that in the absence of gas scattering collisions the collimating effect can be described by geometric shadowing. A Cu cathode with an array of collimating holes machined into the surface was shown to have a collimating effect at high discharge voltages and low current densities. We develop a simple model of the trajectories of ions approaching the cathode to explain the dependence of the angular distribution on the discharge conditions and radial position.
Characteristics Associated With Recurrence Among Women With Ductal Carcinoma In Situ Treated by Lumpectomy (2003)

Nuclear grade is strongly associated with recurrence but not with the type of recurrence. Women with high-nuclear-grade DCIS or DCIS detected by palpation who are treated by lumpectomy alone are at relatively high risk of having an invasive breast cancer recurrence, compared with women with low-nuclear-grade or mammographically detected DCIS, and may be appropriate candidates for additional treatment.
C-Glycosylated Aryl Tins: Versatile Building Blocks for ArylC-Glycoside Glycomimetics (1999)

ABSTRACT C-glycosylated aryl tins have been prepared as versatile building blocks of physiologically stable glycomimetics for glycoepitopes that have been recognized to serve biologically important roles in cell biochemistry.
Taxol metabolism by human liver microsomes: identification of cytochrome P450 isozymes involved in its biotransformation. (1994)

The biotransformation of taxol by human liver was investigated in vitro with microsomes isolated from adult and developing human tissues. In vitro, no metabolism was detected with kidney microsomes, whereas two metabolites were generated by liver microsomes. The most prominent metabolite, termed M5, corresponded to an hydroxylation at the C6 position on the taxane ring, while the other metabolite, termed M4, corresponded to an hydroxylation at the para-position on the phenyl ring at the C3'-position of the C13 side chain. These two taxol derivatives have been shown to be the major metabolites recovered in bile from a patient infused with taxol. Several approaches have been used to identify the cytochrome P450 (CYP) isozymes involved in these reactions. No positive correlation was observed between the in vitro synthesis of these two metabolites, suggesting that two cytochrome P450 isozymes could be involved, although they could not be distinguished by their apparent affinities (Km approximately 15 microM). The formation of metabolite M4 was substantially reduced both by antibody directed against CYP3A and by the addition of CYP3A substrates such as orphenadrine, erythromycin, troleandomycin, and testosterone. Conversely, the formation of metabolite M5 remained unaffected by antibodies against CYP3A and by CYP3A substrates but was sensitive to diazepam inhibition, a preferential substrate of CYP2C. Correlation between CYP2C content or diazepam demethylation and the synthesis of metabolite M5 was highly positive. The formation of metabolite M4 developed during the early postnatal period. In contrast, the synthesis of metabolite M5 rose only after 3 months of age. These data clearly implicate CYP3A in the formation of metabolite M4 and CYP2C in the synthesis of metabolite M5. Microsomes from patients treated with barbiturates and benzodiazepines increased the formation of metabolite M4 to the level of metabolite M5, demonstrating that drug interactions could modify the human metabolism of taxol.
Robotic assisted Laparoscopic partial Nephrectomy for suspected Renal Cell Carcinoma: Retrospective review of surgical outcomes of 35 Cases (2008)

Robotic partial nephrectomy can produce excellent initial results. Further studies should be performed to compare the outcomes to laparoscopic and open operations.