gebhart/patrepeval huggingface dataset:
Interaction with FcγRIIB Is Critical for the Agonistic Activity of Anti-CD40 Monoclonal Antibody (2011)

A high activatory/inhibitory FcγR binding ratio is critical for the activity of mAb such as rituximab and alemtuzumab that attack cancer cells directly and eliminate them by recruiting immune effectors. Optimal FcγR binding profiles of other anti-cancer mAb, such as immunostimulatory mAb that stimulate or block immune receptors, are less clear. In this study, we analyzed the importance of isotype and FcγR interactions in controlling the agonistic activity of the anti-mouse CD40 mAb 3/23. Mouse IgG1 (m1) and IgG2a (m2a) variants of the parental 3/23 (rat IgG2a) were engineered and used to promote humoral and cellular responses against OVA. The mouse IgG1 3/23 was highly agonistic and outperformed the parental Ab when promoting Ab (10-100-fold) and T cell (OTI and OTII) responses (2- to >10-fold). In contrast, m2a was almost completely inactive. Studies in FcγR knockout mice demonstrated a critical role for the inhibitory FcγRIIB in 3/23 activity, whereas activatory FcγR (FcγRI, -III, and -IV) was dispensable. In vitro experiments established that the stimulatory effect of FcγRIIB was mediated through Ab cross-linking delivered in trans between neighboring cells and did not require intracellular signaling. Intriguingly, activatory FcγR provided effective cross-linking of 3/23 m2a in vitro, suggesting the critical role of FcγRIIB in vivo reflects its cellular distribution and bioavailability as much as its affinity for a particular Ab isotype. In conclusion, we demonstrate an essential cross-linking role for the inhibitory FcγRIIB in anti-CD40 immunostimulatory activity and suggest that isotype will be an important issue when optimizing reagents for clinical use.
The Endotoxin‐induced Coagulant Activity of Human Monocytes (1975)

Leucocyte suspensions, exposed to endotoxin in vitro, develop coagulant activity which has been identified as tissue factor. Pure suspensions of polymorphonuclear (PMN) neutrophils, lymphocytes and monocytes were exposed to endotoxin and tested for tissue factor activity after 4 h incubation at 37 degrees C. The results indicate that the monocyte is the cell primarily responsible for the endotoxin-induced coagulant activity of mixed leucocyte suspensions, the small amount of activity demonstrated in PMN neutrophil and in lymphocyte suspensions at high cell concentrations being accounted for by monocyte contamination of less than 1%.
Venous ulcer: epidemiology, physiopathology, diagnosis and treatment (2005)

This review discusses the epidemiology, pathogenesis, diagnosis and current therapeutic options for venous ulcer. Venous ulcer is a severe clinical manifestation of chronic venous insufficiency (CVI). It is responsible for about 70% of chronic ulcers of the lower limbs. The high prevalence of venous ulcer has a significant socioeconomic impact in terms of medical care, days off work and reduced quality of life. Long-term therapeutics are needed to heal venous ulcers and recurrence is quite common, ranging from 54 to 78%. Thrombophlebitis and trauma with long-term immobilization predisposing to deep venous thrombosis are important risk factors for CVI and venous ulcer. The most recent theories about pathogenesis of venous ulcer have associated it with microcirculatory abnormalities and generation of an inflammatory response. Management of venous leg ulcers is based on understanding the pathogenesis. In recent years novel therapeutic approaches for venous ulcers have offered valuable tools for the management of patients with this disorder.
Purification and Properties of Fructosyl-amino Acid Oxidase fromCorynebacteriumsp. 2-4-1 (1989)

Journal Article Purification and Properties of Fructosyl-amino Acid Oxidase from Corynebacterium sp. 2-4-1 Get access Tatsuo Horiuchi, Tatsuo Horiuchi Noda Institute for Scientific Research, Noda, Chiba 278, Japan Search for other works by this author on: Oxford Academic Google Scholar Toshiko Kurokawa, Toshiko Kurokawa Noda Institute for Scientific Research, Noda, Chiba 278, Japan Search for other works by this author on: Oxford Academic Google Scholar Narimasa Saito Narimasa Saito Noda Institute for Scientific Research, Noda, Chiba 278, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 53, Issue 1, 1 January 1989, Pages 103–110, https://doi.org/10.1080/00021369.1989.10869245 Published: 01 January 1989 Article history Received: 12 July 1988 Published: 01 January 1989
Toward Image Guided Robotic Surgery: System Validation (2008)

It was demonstrated that there is a benefit from the augmentation of laparoscopic video with updated preoperative images. Incorporating our image guided system into the da Vinci robotic system improved overall tissue resection, as measured by our metric. Adding image guidance to the da Vinci robotic surgery system may result in the potential for improvements such as the decreased removal of benign tissue while maintaining an appropriate surgical margin.
Clonal heterogeneity in polycythemia vera patients with JAK2 exon12 and JAK2-V617F mutations (2008)

We studied the lineage distribution of JAK2 mutations in peripheral blood of 8 polycythemia vera (PV) patients with exon 12 mutations and in 21 PV patients with JAK2-V617F. Using a quantitative allele discrimination assay, we detected exon 12 mutations in purified granulocytes, monocytes, and platelets of 8 patients studied, but lymphoid cells showed variable involvement and the mutation was absent in T cells. Endogenous erythroid colonies grew in all patients analyzed. One patient displayed erythroid colonies homozygous for the exon 12 mutation with evidence for mitotic recombination on chromosome 9p. In some patients with exon 12 mutations or JAK2-V617F, a proportion of endogenous erythroid colonies were negative for both JAK2 mutations. One patient carried 2 independent clones: one with an exon 12 mutation and a second with JAK2-V617F. The finding of clonal heterogeneity is compatible with the hypothesis that additional clonal events are involved in the pathogenesis of PV.
A Narrow-Waisted Abdominal Aortic Aneurysm Complicating Endovascular Repair (2000)

A narrow waist in an AAA may be considered an additional important anatomical characteristic in assessing suitability for endovascular repair.
A fully integrated Q-enhanced LC filter with 6 dB noise figure at 2.5 GHz in SOI (2004)

Q-enhanced LC filter technology offers a promising approach to remove the off-chip preselect filter still required in current transceivers. To date, previous designs fail to meet the stringent system specifications such as dynamic range and noise figure for existing wireless receivers. This paper presents an innovative prototype design targeted at Bluetooth in silicon-on-insulator (SOI) process. Drawing 5 mA from a 3 V supply, it achieves 17 dB voltage gain, approximately 6 dB noise figure, 153 dB 1-dB compression point dynamic range relative to 1 Hz bandwidth, and 70 MHz bandwidth at 2.5 GHz, suitable for industry applications.
Enantioselective Ribozyme Catalysis of a Bimolecular Cycloaddition Reaction (2000)

Ribozyme-catalyzed Diels–Alder reactions: Through the use of either D- or L-ribozymes the absolute configuration of product 3 can be controlled. An ee value of >95 % is reached in the reaction between 1 and 2. The hexaethylene glycol residue attached to 1 and 3 is an atavism that stems from the in vitro selection of the ribozyme. Reactions with substrates not containing this residue are also catalyzed, albeit with lower ee values.
Safe Use of the CXCR4 Inhibitor ALX40-4C in Humans (2001)

ALX40-4C is a small peptide inhibitor of the chemokine receptor CXCR4 that can inhibit X4 strains of HIV-1. Prior to the discovery of chemokine receptors as the HIV coreceptors, ALX40-4C was used in phase I/II clinical trials to evaluate its therapeutic potential against HIV-1, making ALX40-4C the first anticoreceptor inhibitor to be tested in humans against HIV-1. Patients in the highest dose groups achieved ALX40-4C levels above the effective concentration of the drug for nearly the entire 1-month treatment period. ALX40-4C was well tolerated by 39 of 40 asymptomatic HIV-infected patients, despite the critical role of CXCR4 in normal development and hematopoiesis. No significant or consistent reductions in viral load were observed, but only 12 of the enrolled patients harbored virus types that used CXCR4. We also found that ALX40-4C interacts with the second extracellular loop of CXCR4 and inhibits infection exclusively by blocking direct virus-CXCR4 interactions.
Induction of cytokine expression by leukemia inhibitory factor. (1993)

Biological effects of cytokines are in part determined by their interactions in the regulation of cytokine production. This study analyzes the effects of leukemia inhibitory factor (LIF) on cytokine expression in different cell lineages. Recombinant human LIF increases levels of IL-1 beta, IL-6, and IL-8 mRNA in human articular chondrocytes as demonstrated by Northern blotting. These cytokine mRNAs are detectable as early as 1.3 h after stimulation and reach their maximum after 5 h. The LIF effects are dose dependent and of similar magnitude to those of IL-1. By metabolic labeling and immunoprecipitation it is shown that LIF induces synthesis and secretion of IL-6. IL-6 bioactivity in conditioned media, as measured by the B9 hybridoma proliferation assay, is increased by LIF. Effects of LIF on cytokine expression are not confined to connective tissue cells. By PCR it is shown that human blood monocytes express IL-6 mRNA after stimulation with LIF. An increase in IL-6 mRNA levels is detectable 2 h after stimulation, and this starts to decline by 5 h. The response is of shorter duration as compared with IL-1 beta. In addition to increased mRNA expression, LIF also stimulates release of biologically active IL-6 from blood monocytes. In synoviocytes and neuronal as well as epithelial cell lines, LIF increases IL-1 beta and IL-6 gene expression. In summary, LIF induces cytokine expression in a wide variety of tissues. These results suggest that through the induction of cytokines, LIF can modulate inflammation, immune responses, and connective tissue metabolism, and act as a pathogenetic mediator in different disease states.
COMPARISON OF NEURAL NETWORK AND K-NN CLASSIFICATION METHODS IN VOWEL AND PATELLAR SUBLUXATION IMAGE RECOGNITIONS (1993)

We make a comparision of classification ability between BPN (BackPropagation Neural Network) and k-NN (k-Nearest Neighbor) classification methods. Voice data and patellar subluxation images are used. The result was that the average recognition rate of BPN was 9.2 percent higher than that of the k-NN classification method. Although k-NN classification is simple in theory, classification time was fairly long. Therefore, it seems that real time recognition is difficult. On the other hand, the BPN method has a long learning time but a very short recognition time. Especially if the number of dimensions of the samples is large, it can be said that BPN is better than k-NN in classification ability.
Are all pressure ulcers the result of deep tissue injury? A review of the literature. (2007)

Pressure ulcers are a common problem that significantly contributes to morbidity and mortality. To elucidate the confusion surrounding the origin of pressure ulcers, the question of whether pressure ulcers are caused exclusively by deep tissue injury is addressed. A review of the literature relevant to the pathophysiology and pathogenesis of pressure ulcers is presented and focuses on studies that examine the relationship between mechanical stresses and deep and superficial tissue injury. The studies suggest that deep tissue is more susceptible than superficial tissue to injury caused by externally applied pressure; clinically superficial skin injuries induced by pressure tend to be associated with deep tissue damage; and superficial injuries appear to be caused by factors other than pressure. Based on these observations, pressure ulcers are believed to be the result of deep tissue damage, implying that prevention and treatment of superficial lesions need not necessarily conform to pressure ulcer management that makes eliminating pressure the highest priority. Conversely, the treatment of pressure ulcers should account for the likelihood, even if not visually noted, that deep tissue is involved.
Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond (2008)

A great deal of progress has been made toward developing novel anti-inflammatory agents. In spite of the tremendous advances in the last decade, the design and development of a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge.
Pharmacological studies of meisoindigo: absorption and mechanism of action. (1991)

Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. Experiments have shown the improved absorption of meisoindigo, compared to indirubin to be one of the major reasons for the enhancement of antitumor activity. Studies on the mechanism of meisoindigo action indicate that it strongly inhibits DNA biosynthesis in tumor cells. Strong inhibition of the drug on assembly of microtubule protein was also obtained. By means of FCM technique the effects of meisoindigo on mouse leukemia L1210 cell cycle were examined. Experimental results showed that under the action of meisoindigo the S phase cells accumulated and the traverse of the cells in G2 + M phase to G1 phase may also be blocked to some extent.
Involvement of oxidative mechanisms in blue-light-induced damage to A2E-laden RPE. (2002)

The augmentation of cell death in the presence of D(2)O and the protection afforded by quenchers and scavengers of singlet oxygen, indicates that the generation of singlet oxygen may be involved in the mechanisms leading to the death of A2E-containing RPE cells after blue light illumination. The finding that irradiation also produces oxygen-dependent photochemical changes in A2E, indicates that the effects of singlet oxygen may be mediated either directly or through the generation of reactive photo-products of A2E.
Inertial sensing in ambulatory back load estimation (2002)

Inertial sensing techniques are applied to ambulatory assess back movement in a system for ambulatory estimation of low back load. A combination of a accelerometer and a miniature solid state rate gyroscope was proposed and validated against movement data recorded simultaneously with a 3D video based movement analysis system. The inertial sensing technique appeared to estimate absolute back inclination angle with a typical relative error of /spl plusmn/10%.
Cloning of Cardiac, Kidney, and Brain Promoters of the Feline ncx1 Gene (1997)

The Na+-Ca2+ exchanger (NCX1) plays a major role in calcium efflux and therefore in the control and regulation of intracellular calcium in the heart. The exchanger has been shown to be regulated at several levels including transcription. NCX1 mRNA levels are up-regulated in both cardiac hypertrophy and failure. In this work, the 5'-end of the ncx1 gene has been cloned to study the mechanisms that mediate hypertrophic stimulation and cardiac expression. The feline ncx1 gene has three exons that encode 5'-untranslated sequences that are under the control of three tissue-specific promoters. The cardiac promoter drives expression in cardiocytes, but not in mouse L cells. Although it contains at least one enhancer (-2000 to -1250 base pairs (bp)) and one or more negative elements (-1250 to -250 bp), a minimum promoter (-250 to +200 bp) is sufficient for cardiac expression and alpha-adrenergic stimulation.
Elucidation of the Methylerythritol Phosphate Pathway for Isoprenoid Biosynthesis in Bacteria and Plastids. A Metabolic Milestone Achieved through Genomics (2002)

Plants synthesize an enormous variety of metabolites that can be classified into two groups based on their function: primary metabolites, which participate in nutrition and essential metabolic processes within the plant, and secondary metabolites (also referred to as natural products), which
Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency (1992)

An efficient expression system in Escherichia coli for several biologically active insulin-like growth factor-I (IGF-I) fusion peptide analogues is described. These novel IGF-I fusion protein analogues have properties that make them very useful reagents in the investigation of IGF-I action. The analogues comprise an IGF-I sequence and the first 11 amino acids of methionyl porcine growth hormone (pGH) and include [Met1]-pGH(1-11)-Val-Asn-IGF-I, which contains the authentic IGF-I sequence, and two analogues, [Met1]-pGH(1-11)-Val-Asn-[Gly3]-IGF-I and [Met1]-pGH(1-11)-Val-Asn-[Arg3]-IGF-I, where Glu-3 in the human IGF-I sequence has been replaced by Gly or Arg respectively. The three peptides are referred to as Long IGF-I, Long [Gly3]-IGF-I or Long [Arg3]-IGF-I depending on the IGF-I sequence present. Production of the purified fusion peptides was aided by folding the reduced and denatured fusion peptide sequence under conditions that gave very high yields of biologically active product. Introduction of a hydrophobic N-terminal extension peptide appears to facilitate the correct folding of the IGF-I analogues compared with that obtained previously when folding normal-length IGFs. The biological activities of the IGF-I fusion peptides were compared with authentic IGF-I and the truncated analogue, des(1-3)IGF-I. In L6 rat myoblasts, all the analogues were more potent than authentic IGF-I in their abilities to stimulate protein and DNA synthesis and inhibit protein breakdown. In H35 hepatoma cells, where the IGFs act through the insulin receptor, the Long IGF-I analogues maintained a similar potency relative to IGF-I as was observed in the L6 myoblasts. The order of biological potency in cell lines secreting IGF-binding proteins (IGFBPs) into the medium was Long [Arg3]-IGF-I-des(1-3)IGF-I greater than Long [Gly3]-IGF-I greater than Long IGF-I greater than IGF-I. In chicken embryo fibroblasts, a cell line that does not secrete detectable IGFBPs into the medium, Long [Arg3]-IGF-I, was less potent than IGF-I. Investigation of receptor and IGFBP association by these analogues reinforced our previous findings that N-terminal analogues of IGF-I show increased biological potency due to changes in the degree of their IGFBP interactions.
Interleukin-1 alpha administered after autologous transplantation: a phase I/II clinical trial (1994)

Abstract Interleukin-1 alpha (IL-1 alpha) can act as both a hematopoietic growth factor and a stimulant of cellular and humoral immune responses. To promote acceleration of hematologic recovery and induce immune antitumor activity, we initiated a phase I/II dose escalation trial of 6-hour daily infusions of recombinant human IL-1 alpha after autologous transplantation. Forty patients with Hodgkin's disease (n = 9) and non- Hodgkin's lymphoma (n = 31) transplanted with unmobilized autologous peripheral blood stem cells or bone marrow stem cells received daily 6- hour infusions of IL-1 alpha (day 0 to day +13) at daily doses between 0.1 to 10 micrograms/m2/d; 7 patients received only 7 planned days of IL-1 alpha (day 0 through 6). Most patients received all 14 days of therapy, although 5 patients discontinued treatment early (after 1 to 6 doses) because of fever and severe chills. Toxicity included IL-1 alpha- related fever (occurring on a median of 9 of 14 treatment days), fatigue, and severe chills. Hypotension was dose-limiting and led to discontinuation of IL-1 alpha in both patients receiving 10 micrograms/m2/d. IL-1 alpha-treated patients receiving 3.0 micrograms/m2/d (the maximum tolerated dose) achieved neutrophil recovery (absolute neutrophil count greater than 500/microL) significantly earlier (median, 12 days; range, 11 to 27) than untreated control patients or those receiving IL-1 alpha at 0.1 to 1.0 micrograms/m2/d (median, 27; range, 9 to 63; P &lt; .0001). In addition, the IL-1 alpha patients' bone marrows at day +14 were significantly enriched with committed myeloid progenitor cells. Strong trends to earlier freedom from red blood cell (P = .06) and platelet (P = .09) transfusions were also noted after IL-1 alpha treatment. This earlier hematopoietic engraftment after 3.0 micrograms/m2/d IL-1 alpha allowed earlier hospital discharge (median, 25 v 37 days for control or low- dose IL-1 alpha patients [P &lt; .0001]) and a concomitant reduction (by $38,000) in median hospital charges (P = .01). The clinical toxicities of IL-1 alpha infusion are substantial, though not life-threatening. The accelerated hematopoiesis and immune response activation observed in this trial suggest the value of its further investigation in controlled trials and perhaps in combination with other hemopoietins after transplantation.
Local Defectivity Control of 2D Self‐Assembled Block Copolymer Patterns (2007)

Surface patterning of copolymers via self-assembly is achieved by substrate design. The figure shows a polystyrene-block-poly(methyl methacrylate) symmetric diblock copolymer confined in a tapered structure. Engineering the channel structure provides local defectivity control for defect-free striped lamellar patterns at the nanometer scale.
Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. II. Biased T cell receptor V beta expression predominates in spinal cord infiltrating T cells (1992)

The immune response of Lewis rat lymph node T cells to guinea pig myelin basic protein (GP-BP) in experimental allergic encephalomyelitis is directed primarily against a region of basic protein encompassed by residues 72-89. T cells that respond to this epitope are restricted by the RT1.B class II molecule of the MHC and use V beta 8.2 exclusively in their TCR. A second region of GP-BP, residues 87-99, also induces experimental allergic encephalomyelitis in Lewis rats but this response is restricted primarily by RT1.D. Elsewhere we describe the biologic characteristics of T cell clones responding to the synthetic peptide, s87-99, and to a related peptide, s85-99. We present a detailed analysis of TCR V beta gene expression among these clones, derived from the lymph node and spinal cord of immunized animals, and among spinal cord derived T cell clones reactive to GP-BP 72-89. We find that spinal cord-derived clones, reactive to s85-99 and to s87-99, use V beta 6 predominantly. In contrast, T cell clones derived from lymph nodes and reactive to the same peptides express multiple V beta genes including V beta 6. This difference in heterogeneity of V beta usage at the clonal level is also seen in T cell lines derived from spinal cord and immune lymph node. DNA sequence comparison of the CDR3 regions in V beta 6+ spinal cord clones revealed a conserved amino acid motif also found in the majority of V beta 6 sequences from the spinal cord anti-s85-99 line. Although V beta 6 was expressed in some lymph node-derived clones, only one contained a CDR3 region similar to that seen in spinal cord isolates. All spinal cord-derived T cell clones reactive to GP-BP 72-89 used V beta 8.2 and most (five of six) contained the AspSer residues in CDR3 previously shown to be associated with V beta 8.2 receptors expressed by the majority of lymph node T cells responding to GP-BP 72-89. These data indicate that TCR V beta usage in peripheral T cells responding to an autoantigen does not always predict the V beta usage among T cells at the site of an autoimmune attack. Possible explantations for the relative homogeneity in TCR V beta expression seen in T cell clones derived from the spinal cord are discussed.