gebhart/patrepeval huggingface dataset:
Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis (2000)

The chimeric anti-CD20 MAb rituximab has recently become a treatment of choice for low-grade or follicular non-Hodgkin's lymphomas (FL) with a response rate of about 50%. In this report, we have investigated the mechanism of action of rituximab on 4 FL and 1 Burkitt's lymphoma (BL) cell lines, 3 fresh FL samples and normal B cells in vitro. Rituximab efficiently blocks the proliferation of normal B cells, but not that of the lymphoma lines. We did not detect significant apoptosis of the cell lines in response to rituximab alone. All cell lines were targets of antibody-dependent cellular cytotoxicity (ADCC). On the other hand, human complement-mediated lysis was highly variable between cell lines, ranging from 100% lysis to complete resistance. Investigation of the role of the complement inhibitors CD35, CD46, CD55, and CD59 showed that CD55, and to a lesser extent CD59, are important regulators of complement-mediated cytotoxicity (CDC) in FL cell lines as well as in fresh cases of FL: Blocking CD55 and/or CD59 function with specific antibodies significantly increased CDC in FL cells. We conclude that CDC and ADCC are major mechanisms of action of rituximab on B-cell lymphomas and that a heterogeneous susceptibility of different lymphoma cells to complement may be at least in part responsible for the heterogeneity of the response of different patients to rituximab in vivo. Furthermore, we suggest that the relative levels of CD55 and CD59 may become useful markers to predict the clinical response. (Blood. 2000;95:3900-3908)
Increased aryl hydrocarbon receptor expression in patients with allergic rhinitis (2013)

The results suggested that the AhR may be one of the mechanisms underlying the Th17 response during the pathogenesis of AR and AhR levels were closely related to clinical severity in all AR patients. Additionally, ITE may represent a new drug candidate in the treatment of AR.
Multicenter, Randomized Trial for Stage IIIB or IV Non–Small-Cell Lung Cancer Using Weekly Paclitaxel and Carboplatin Followed by Maintenance Weekly Paclitaxel or Observation (2003)

Arm 1, paclitaxel 100 mg/m2 weekly for 3 of 4 weeks with carboplatin (AUC = 6) administered on day 1, demonstrates the most favorable therapeutic index in patients with advanced NSCLC.
Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol (2011)

Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis. We report the final results of HLH-94, the largest prospective diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients with familial, persistent, or recurrent disease. Altogether, 249 patients fulfilled inclusion criteria and started HLH-94 therapy (July 1994-December 2003); 227 (91%) were followed-up for ≥ 5 years. At 6.2 years median follow-up, estimated 5-year probability of survival was 54% ± 6%. Seventy-two patients (29%) died before HSCT, 64 within 1 year, 97% of whom had active disease. In 124 patients who underwent HSCT, 5-year survival was 66 ± 8%; tendency to increased survival (P = .064) in patients with nonactive disease at HSCT. Patients with familial disease had a 5-year survival of 50% ± 13%; none survived without HSCT. Patients deceased during the first 2 months more often had jaundice, edema, and elevated creatinine. Forty-nine patients (20%) were alive without signs of HLH activity and off-therapy > 1-year without HSCT; they presented at older age (P < .001), were more often female (P = .011), and less often had CNS disease (P < .001) or hepatomegaly (P = .007). To conclude, HLH-94 chemoimmunotherapy has considerably improved outcome in HLH. Collaborative efforts are needed to further reduce early mortality, HSCT-related mortality, and neurologic late effects.
Generation and collection of photocarriers in dilute nitride GaInNAsSb solar cells (2015)

Abstract An improved photocurrent production is demonstrated in dilute nitride GaInNAsSb solar cells grown by molecular beam epitaxy. The photovoltaic properties were investigated by increasing the thickness of GaInNAsSb layers from 1.0 to 3.0 µm. The amount of photon absorption increased with increasing thickness. Yet an incomplete photocarrier collection was observed in the 2.0‐ and 3.0‐µm‐thick GaInNAsSb devices. This feature is due to a partial lack of electric field in the GaInNAsSb region. In order for complete carrier collection aided by the electric field, the background‐doping level should be as low as ~10 14 cm −3 in a thick undoped ‐GaInNAsSb absorption layer. Here, the effectiveness of annealing on improving the field‐assisted carrier collection is shown. This is ascribed to a decrease of the background doping in the GaInNAsSb layer. In a properly designed device for a 1.0‐eV GaInNAsSb cell, it is demonstrated that the external quantum efficiency can reach as high as 90% at wavelengths longer than the GaAs bandgap. Copyright © 2015 John Wiley &amp; Sons, Ltd.
FDTD characterization of evanescent modes-multimode analysis of waveguide discontinuities (2000)

In this paper, a finite-difference time-domain numerical dispersion relation for evanescent waves is derived, and its impact on the modeling accuracy is studied. The numerical evanescent constant is found to differ from the analytical one. As a result, a correction must be used to compute discontinuity parameters. This influences the reference plane chosen for the analysis of propagating modes. Moreover, on calculating multimode transmission and reflection coefficients, the dispersion for evanescent higher order modes is determinant. The dispersive relation is derived, discussed, and used to correct the evanescent constants for the multimode analysis of a waveguide discontinuity.
High dose methylprednisolone therapy for the treatment of severe systemic lupus erythematosus (2007)

The pharmacological armamentarium for the treatment of SLE is expanding and a number of novel therapies are currently under investigation. In spite of this, steroid therapy remains the cornerstone of treatment and intravenous methylprednisolone (IVMP) is still widely used in clinical practice. There is however surprisingly little evidence on which to define its precise role. The objective of this review was to consider the published evidence relating to the use of IVMP in SLE patients and also to identify open questions that still need to be answered with regard to its use. In acute flares, IVMP induces rapid suppression of acute inflammation. There is not however a strong evidence base to support the use of high doses compared to low IVMP doses or oral prednisolone. In maintenance regimes, secondary analyses suggest that IVMP may confer additional long-term renal survival over oral steroids as part of a cyclophosphamide regime. Therefore, in addition to the evaluation of novel therapies for SLE, better evidence to define the precise role of IVMP in SLE is still required.
Eradication of hepatic metastases of carcinoma H-59 by combination chemoimmunotherapy with liposomal muramyl tripeptide, 5-fluorouracil, and leucovorin. (1992)

We have investigated the effect of a combined chemoimmunotherapy protocol with liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE), 5-fluorouracil (5-FU), and 5-formyltetrahydrofolate (leucovorin) on the growth of hepatic metastases using carcinoma H-59, a liver-homing subline of the Lewis lung carcinoma (P. Brodt, Cancer Res., 46: 2442-2448, 1986). C57BL/6 mice inoculated with the tumor cells via the intrasplenic route received three i.v. injections of liposomal MTP-PE, the first of which was administered 3 days prior to tumor cell inoculation. Chemotherapy with 5-FU and leucovorin at the maximal tolerated doses (30 mg/kg per injection) was initiated immediately after tumor inoculation and continued on alternate days for a total of 4 injections. The incidence of liver metastases in animals which received the combined therapy was compared to that in animals treated with chemotherapy or immunotherapy alone. We found that while the number of liver metastases was reduced in all of the treatment groups as compared to control untreated or placebo-treated animals, the combined effect of 5-FU leucovorin and liposomal MTP-PE was significantly better than that of chemotherapy or immunotherapy alone. This was reflected in a reduced incidence (70% as compared to 100% in all other groups) and in a significant reduction in the number and size of the liver nodules. Our results suggest that the efficacy of 5-FU and leucovorin in the treatment of hepatic metastases could be significantly augmented by the addition of the liposome-encapsulated immunoadjuvant MTP-PE.
Platelet Lysate Consisting of a Natural Repair Proteome Supports Human Mesenchymal Stem Cell Proliferation and Chromosomal Stability (2010)

With favorable regenerative and immunotolerant profiles, patient-derived human mesenchymal stem cells (hMSCs) are increasingly considered in cell therapy. Derived from bone marrow (BM) and standardized with culture in fetal bovine serum (FBS), translation of hMSC-based approaches is impeded by protracted expansion times, risk of xenogenic response, and exposure to zoonoses. Here, human platelet lysate adherent to good manufacturing practices (GMP-hPL) provided a nonzoonotic adjuvant that enhanced the capacity of BM-hMSC to proliferate. The nurturing benefit of GMP-hPL was generalized to hMSC from adipose tissue evaluated as an alternative to bone marrow. Long-term culture in GMP-hPL maintained the multipotency of hMSC, while protecting against clonal chromosomal instability detected in the FBS milieu. Proteomic dissection identified TGF-β, VEGF, PDGF, FGF, and EGF as highly ranked effectors of hPL activity, revealing a paradigm of healing that underlies platelet lysate adjuvancy. Thus, GMP-adherent human platelet lysate accelerates hMSC proliferation with no chromosomal aberrancy, through an innate repair paradigm.
Effect of Solvent and pH on the Structure of PAMAM Dendrimers (2005)

We report various structural and conformational properties of generations 4, 5, and 6 PAMAM (polyamidoamine) dendrimer [EDA (ethylenediamine) core)] at various protonation levels through extensive molecular dynamics (MD) simulations in explicit solvent. The presence of solvent leads to swelling of the dendrimer (by 33% for G5 compared to the case of no solvent). We find that decreasing the solution from high pH (∼10, no protonation) to neutral (∼7, only primary amines protonated) to low pH (∼4, tertiary amines also protonated) changes the radius of gyration of G5 from 21 to 22 to 25 Å, respectively. We also report such other structural quantities as radial density, distribution of terminal groups, solvent accessible surface area and volume, shape, and structure factors (to compare with SAXS and SANS experiments) at various pH conditions. We find significant back-folding of the outer subgenerations in the interior of the molecules at all levels of pH, contrary to original expectations and some SANS experiments but in agreement with other SANS experiments. We find significant water penetration inside the dendrimer, with ∼3 water/tertiary amine for high pH and ∼6 water/tertiary amine for low pH (all for G5). This indicates that the interior of the dendrimer is quite open with internal cavities available for accommodating guest molecules, suggesting using PAMAM dendrimer for guest−host applications. This estimate of internal waters suggests that sufficient water is available to facilitate metal ion binding.
The Insulin-like Growth Factor System in Hematopoietic Cells (2002)

The insulin-like growth factor (IGF) system regulates proliferation and differentiation of hematopoietic cells. IGFs exert their effects through specific receptors on growing and differentiating blood cells as they emerge from their small pool of ancestral stem cells. The IGF system is complex as both stimulating and inhibiting effects occur by interaction of IGFs and IGF-binding proteins (IGFBPs). IGFs stimulate erythrocytes and lymphocytes but also promote leukemic hematopoietic cell proliferation. IGF-I appears to be correlated with hemoglobin levels in anemia and could also be of benefit for patients with bone marrow aplasia after transplantation. Hypersensitivity to IGF-I has been implicated as an underlying cause of polycythemia vera. Loss of imprinting of IGF-II is found in acute myeloid leukemia and myelodysplastic syndrome. Apoptosis of hematopoietic cells is significantly reduced by IGF-I involving an intriguing signal transduction pathway. IGFs could therefore, although not classical hematopoietic growth factors, be of benefit for patients with diverse hematopoietic disorders.
An Improved Synthesis of 2-Acetamido-2-deoxy-D-gluconohydroximolactone (PUGNAc), A Strong Inhibitor ofβ-N-Acetylglucosaminidases (2000)

O-(2-Acetamido-3,4,6-tri-O-acetyl-D-glucopyranosylidene)amino N-phenylcarbamate (1), an established inhibitor of β-N-acetylglucosaminidases, has been prepared by an improved six-step synthesis from N-acetyl-D-glucosamine.
Evidence for two evolutionary lineages of highly pathogenic Yersinia species (1995)

Sensitivity to Yersinia pestis bacteriocin pesticin correlates with the existence of two groups of human pathogenic yersiniae, mouse lethal and mouse nonlethal. The presence of the outer membrane pesticin receptor (FyuA) in mouse-lethal yersiniae is a prerequisite for pesticin sensitivity. Genes that code for FyuA (fyuA) were identified and sequenced from pesticin-sensitive bacteria, including Y. enterocolitica biotype 1B (serotypes O8; O13, O20, and O21), Y. pseudotuberculosis serotype O1, Y. pestis, two known pesticin-sensitive Escherichia coli isolates (E. coli Phi and E. coli CA42), and two newly discovered pesticin-sensitive isolates, E. coli K49 and K235. A 2,318-bp fyuA sequence was shown to be highly conserved in all pesticin-sensitive bacteria, including E. coli strains (DNA sequence homology was 98.5 to 99.9%). The same degree of DNA homology (97.8 to 100%) was established for the sequenced 276-bp fragment of the irp2 gene that encodes high-molecular-weight protein 2, which is also thought to be involved in the expression of virulence by Yersinia species. Highly conserved irp2 was also found in all pesticin-sensitive E. coli strains. On the basis of the fyuA and irp2 sequence homologies, two evolutionary groups of highly pathogenic Yersinia species can be established. One group includes Y. enterocolitica biotype 1B strains, while the second includes Y. pestis, Y. pseudotuberculosis serotype O1, and irp2-positive Y. pseudotuberculosis serotype O3 strains. E. coli Phi, CA42, K49, and K235 belong to the second group. The possible proximity of these two iron-regulated genes (fyuA and irp2), as well as their high levels of sequence conservation and similar G+C contents (56.2 and 59.8 mol%), leads to the assumption that these two genes may represent part of an unstable pathogenicity island that has been acquired by pesticin-sensitive bacteria as a result of a horizontal transfer.
Polyclonal antibodies: a cheap and efficient tool for screening of enantioselective catalysts (2012)

Enantioselective polyclonal antibodies have been produced and characterized to develop a high-throughput screening method for lipase activity fingerprinting, with a view to the enantioselective hydrolysis of azlactones.
Mutational landscape of antibody variable domains reveals a switch modulating the interdomain conformational dynamics and antigen binding (2017)

Somatic mutations within the antibody variable domains are critical to the immense capacity of the immune repertoire. Here, via a deep mutational scan, we dissect how mutations at all positions of the variable domains of a high-affinity anti-VEGF antibody G6.31 impact its antigen-binding function. The resulting mutational landscape demonstrates that large portions of antibody variable domain positions are open to mutation, and that beneficial mutations can be found throughout the variable domains. We determine the role of one antigen-distal light chain position 83, demonstrating that mutation at this site optimizes both antigen affinity and thermostability by modulating the interdomain conformational dynamics of the antigen-binding fragment. Furthermore, by analyzing a large number of human antibody sequences and structures, we demonstrate that somatic mutations occur frequently at position 83, with corresponding domain conformations observed for G6.31. Therefore, the modulation of interdomain dynamics represents an important mechanism during antibody maturation in vivo.
Study of the Five Rickettsia prowazekii Proteins Annotated as ATP/ADP Translocases (Tlc): Only Tlc1 Transports ATP/ADP, While Tlc4 and Tlc5 Transport Other Ribonucleotides (2006)

The obligate intracytoplasmic pathogen Rickettsia prowazekii relies on the transport of many essential compounds from the cytoplasm of the eukaryotic host cell in lieu of de novo synthesis, an evolutionary outcome undoubtedly linked to obligatory growth in this metabolite-replete niche. The paradigm for the study of rickettsial transport systems is the ATP/ADP translocase Tlc1, which exchanges bacterial ADP for host cell ATP as a source of energy, rather than as a source of adenylate. Interestingly, the R. prowazekii genome encodes four open reading frames that are highly homologous to the well-characterized ATP/ADP translocase Tlc1. Therefore, by annotation, the R. prowazekii genome encodes a total of five ATP/ADP translocases: Tlc1, Tlc2, Tlc3, Tlc4, and Tlc5. We have confirmed by quantitative reverse transcriptase PCR that mRNAs corresponding to all five tlc homologues are expressed in R. prowazekii growing in L-929 cells and have shown their heterologous protein expression in Escherichia coli, suggesting that none of the tlc genes are pseudogenes in the process of evolutionary meltdown. However, we demonstrate by heterologous expression in E. coli that only Tlc1 functions as an ATP/ADP transporter. A survey of nucleotides and nucleosides has determined that Tlc4 transports CTP, UTP, and GDP. Intriguingly, although GTP was not transported by Tlc4, it was an inhibitor of CTP and UTP uptake and demonstrated a K(i) similar to that of GDP. In addition, we demonstrate that Tlc5 transports GTP and GDP. We postulate that Tlc4 and Tlc5 serve the primary function of maintaining intracellular pools of nucleotides for rickettsial nucleic acid biosynthesis and do not provide the cell with nucleoside triphosphates as an energy source, as is the case for Tlc1. Although heterologous expression of Tlc2 and Tlc3 was observed in E. coli, we were unable to identify substrates for these proteins.
Peginterferon-α2b and ribavirin (2004)

Hepatitis C virus infection is among the leading causes of chronic liver disease in the USA and has a worldwide prevalence of approximately 300 million people. Chronic hepatitis C virus is the most common indication for liver transplantation in the USA. Due to the chronic nature of hepatitis C virus infection, these numbers are expected to grow fourfold in the next decade. Interferon-alpha(2b) monotherapy followed by combination therapy with ribavirin have been used to treat chronic hepatitis C virus with limited success. The development of pegylated interferon-alpha(2b), (Peg-intron, Schering-Plough) instituted the next chapter in hepatitis C virus therapy. The demonstration of its safety and efficacy led to a major trial studying coadministration with ribavirin for compensated chronic hepatitis C virus infection. Pegylated interferon combination therapy has improved efficacy over standard interferon combination therapy without an increase in adverse effects. This article reviews the data regarding pegylated interferon-alpha(2b) with ribavirin therapy. The pharmacokinetics and pharmacodynamics of combination therapy will be presented along with clinical trial data. The efficacy and ease of usage of Pegintron and ribavirin support its use for chronic hepatitis C virus infection.
Restoration in Layered Architectures with a WDM Mesh Optical Layer (2002)

This work provides an overview and a comparison of various techniques used to restore lightpaths in a layered architecture. The comparison takes into consideration figures of merit such as speed of restoration and redundant capacity. The objective is to optimize the performance of the network (including fast end-to-end service survivability, minimizing the spare resources required) under all circumstances, using available resources and implemented mechanisms.
The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and inhibit O2 generation, respectively. (1990)

Occupancy of specific receptors on neutrophils by adenosine or its analogues diminishes the stimulated release of toxic oxygen metabolites from neutrophils, while paradoxically promoting chemotaxis. We now report evidence that two distinct adenosine receptors are found on neutrophils (presumably the A1 and A2 receptors of other cell types). These adenosine receptors modulate chemotaxis and O2- generation, respectively. N6-Cyclopentyladenosine (CPA), a selective A1 agonist, promoted neutrophil chemotaxis to the chemoattractant FMLP as well as or better than 5'N-ethylcarboxamidoadenosine (NECA). In contrast, CPA did not inhibit O2- generation stimulated by FMLP. Pertussis toxin completely abolished promotion of chemotaxis by CPA but enhanced inhibition by NECA of O2- generation. Disruption of microtubules by colchicine or vinblastine also abrogated the enhancement by NECA of chemotaxis whereas these agents did not markedly interfere with inhibition by NECA of O2- generation. FMLP receptors, once they have bound ligand, shift to a high affinity state and become associated with the cytoskeleton. NECA significantly increased association of [3H]FMLP with cytoskeletal preparations as it inhibited O2-. Disruption of microtubules did not prevent NECA from increasing association of [3H]FMLP with cytoskeletal preparations. Additionally, CPA (A1 agonist) did not increase binding of [3H]FMLP to the cytoskeleton as well as NECA (A2 agonist). These studies indicate that occupancy of one class of adenosine receptors (A1) promotes chemotaxis by a mechanism requiring intact microtubules and G proteins whereas engagement of a second class of receptors (A2) inhibits O2- generation. Signalling via A2 receptors is independent of microtubules, insensitive to pertussis toxin and is associated with binding of [3H]FMLP to cytoskeletal preparations.
Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer (2009)

Prostvac is a prostate cancer vaccine regimen consisting of a recombinant vaccinia vector as a primary vaccination, followed by multiple booster vaccinations employing a recombinant fowlpox vector. Both vectors contain the transgenes for prostate-specific antigen (PSA) and multiple T-cell co-stimulatory molecules (TRICOM). The PSA-TRICOM vaccines infect antigen-presenting cells (APCs) and generate proteins that are expressed on the surface of the APCs in an immune context. The interaction of these APCs with T cells initiates a targeted immune response and T cell-mediated tumor cell destruction. Preliminary clinical trials have indicated negligible toxicity, and Phase II trials have suggested a survival benefit after treatment with Prostvac, especially in patients with indolent disease characteristics. Preclinical and clinical data indicate that radiation, hormonal therapy, and chemotherapy may be combined with Prostvac to enhance the vaccine's efficacy. Additional strategies are in development to further enhance the clinical benefits of Prostvac, and a Phase III trial is being planned in metastatic castration-resistant prostate cancer.