gebhart/patrepeval huggingface dataset:
Characterization of MDX-1401, a Human Anti-CD30 Antibody with Enhanced Effector Function, for Therapy of Malignant Lymphoma. (2008)

Abstract Therapeutic monoclonal antibodies kill target cells by multiple mechanisms including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent phagocytosis (ADP), complement-dependent cytotoxicity (CDC), and direct induction of apoptosis. Antibody binding to FcgRIIIA (CD16), which is expressed on NK cells, macrophages, and CD8+ cells, is essential for ADCC. MDX-1401 is a fully human monoclonal antibody of IgG1 (kappa) isotype that binds to human CD30. This second generation anti-CD30 antibody was derived from parental antibody MDX-060 but differs in that the oligosaccharides of the IgG1 lack fucose, a property that conveys increased antibody affinity for Fc receptor CD16 (FcgRIIIa) and thus stimulates both more potent and efficacious ADCC than a fucosylated IgG1. The KD of the parental antibody for CD30 expressed on L540 Hodgkin’s lymphoma cells is approximately 1.4 nM while the KD of MDX-1401 is 1.9 nM, demonstrating that binding affinity for antigen are nearly identical. However, the EC50 for MDX-1401 binding to CD16-transfected cells is approximately 3 nM compared to barely detectable binding by parental antibody, confirming that the absence of fucose conveys increased affinity for FcgRIIIa. Data is presented that demonstrates MDX-1401 has significantly improved potency and efficacy in an ADCC assay as evidenced by a decrease in EC50 as well as an increase in maximum specific lysis. Importantly, the enhanced ADCC activity is observed among a large panel of cell lines with varying numbers of CD30 receptors per cell, including one cell line with low antigen expression in which parental antibody failed to induce ADCC. MDX-1401 enhances ADCC activity with all polymorphic variants including lower affinity FcgRIIIa Phe/Phe158 and FcgRIIIa Phe/Val158 effector cells. Furthermore, MDX-1401 is efficacious in inhibiting growth of CD30+ tumor xenografts in mice. The low doses of antibody required for ADCC activity irrespective of donor genotype, the capacity to mediate ADCC of target cells expressing low levels of CD30, and increased in vivo efficacy support the development of MDX-1401 for treatment of malignant lymphoma. Phase 1 studies in subjects with Hodgkin’s lymphoma are currently underway.
Abstract 5515: Proteomics, Metabolomics and Immunomics on Human Microparticles Derived from Atherosclerotic Plaques (2008)

Background. Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their protein and metabolite composition. Methods and Results. In this study, we performed a combined proteomic, metabolomic and immunomic analysis to obtain insights into the role of MPs in atherogenesis. MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution NMR spectroscopy and antibody reactivity was assessed against combinatorial antigen libraries. The proteomic analysis resulted in the identification of 151 unique proteins in MPs, including surface antigens consistent with their leukocyte origin, ie. CD14, CD11c, CD18, CD29, CD51, CD36 and major histocompatibility complex class I and II. Moreover, MPs had metabolite profiles, which were distinct from atherosclerotic plaques. When proteins on the MP surface were fluorescence tagged and separated by 2-dimensional gel electrophoresis, immunoglobulins were not surface-labeled. Subsequent flow cytometry analysis on perme-abilized and non-permeabilized plaque MPs confirmed that immunoglobulins were trapped inside plaque-derived MPs. Notably, co-labelling for CD14 and IgG revealed that over 90% of the IgG containing MPs were CD14 positive, indicating a macrophage origin. Screening against a combinatorial antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques, but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A and the Gal-alpha-(1,3)-Gal linkage, the antigen responsible for hyperacute rejection in xenotransplantation. Conclusions. This study provides the first evidence that immune complexes in human atherosclerotic lesions exist within MPs derived from plaque macrophages, that their portfolio is different from circulating antibodies in plasma and that common carbohydrates are important antigens in atherosclerosis. Thus, besides being a determinant of plaque thrombogenicity, MPs might play a previously unrecognized role in the containment of immune complexes, which is likely to influence plaque stability.
Preparation of the Core Structure ofAspidospermaandStrychnosAlkaloids from Aryl Azides by a Cascade Radical Cyclization (2016)

A novel approach to prepare the core structure of Aspidosperma and Strychnos alkaloids is described. The strategy is based on a cyclization cascade involving the formation of quaternary carbon center followed by trapping of the radical intermediate by an aryl azide to build the 5-membered ring of the pyrrolocarbazole system. This reaction is run with triethylborane without the need for any hydrogen atom donor such as a tin hydride or tris(trimethylsilyl)silane, and it furnishes the tetracyclic framework as a single diastereomer. The influence of different N-protecting groups on the starting iodoacetamide has been examined.
15-PGDH Inhibition Activates the Splenic Niche to Promote Hematopoietic Regeneration (2020)

Abstract The splenic microenvironment regulates hematopoietic stem and progenitor cell (HSPC) function, particularly during demand-adapted hematopoiesis, however practical strategies to enhance splenic support of transplanted HSPCs have proven elusive. We have previously demonstrated that inhibiting 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using the small molecule (+)SW033291 (PGDHi), increases bone marrow (BM) prostaglandin E2 (PGE2) levels, expands HSPC numbers, and accelerates hematologic reconstitution following BM transplantation (BMT) in mice. Here we demonstrate that the splenic microenvironment, specifically 15-PGDH high-expressing macrophages (MΦs), megakaryocytes (MKs), and mast cells (MCs), regulates steady-state hematopoiesis and potentiates recovery after BMT. Notably, PGDHi-induced neutrophil, platelet, and HSPC recovery were highly attenuated in splenectomized mice. PGDHi induced non-pathologic splenic extramedullary hematopoiesis at steady-state, and pre-transplant PGDHi enhanced the homing of transplanted cells to the spleen. 15-PGDH enzymatic activity localized specifically to MΦs, MK lineage cells, and MCs, identifying these cell types as likely coordinating the impact of PGDHi on splenic HSPCs. These findings suggest that 15-PGDH expression marks novel HSC niche cell types that regulate hematopoietic regeneration. Therefore, PGDHi provides a well-tolerated strategy to therapeutically target multiple HSC niches and to promote hematopoietic regeneration and improve clinical outcomes of BMT.
Hydrophobically Functionalized Chitosan Particles (2009)

Abstract Particles of chitosan have a very polar surface, and thus they are easily wetted by water and also dissolve in acidic media. The hydroxyl and amino groups offer a high potential for grafting reactions. Aldehydes and carbonic acid derivatives were covalently grafted, preferably onto the amino groups. The reactions were carried out in solution as homogeneous phase reactions as well as on the particle surfaces as heterogeneous phase reactions. Covalently bonded alkyl chains impart the chitosan molecules with hydrophobic properties. We employed different methods such as NMR, XPS, elemental analysis and FT-IR spectroscopy to study the reactions and to estimate the degree of functionalization. The wetting behavior of the particles was investigated by a modified Wilhelmy technique, where an adhesive tape completely coated with the particles was dipped in water. Some of the samples having a high degree of functionalization showed super-hydrophobic surface properties. The observed super-hydrophobic effect results from a combination of the hydrophobic properties of the modified particles and the roughness of the particle coating. Keywords: CHITOSANGRAFTING OF ALDEHYDES AND CARBONIC ACID DERIVATIVESNMRXPSFT-IRHYDROPHOBIZATIONSUPER-HYDROPHOBICITYWILHELMY TECHNIQUE
An Approach to Compact, Wet Gas Compression (2010)

In recent years, several papers have been written regarding the use of centrifugal compression technology to handle applications in which the process gas entering the equipment contains a significant amount of liquids, and can therefore be considered a wet gas. One such application that is currently being considered by many oil and gas operators is the installation of processing and compression equipment on the sea bed, to directly handle the process gas stream in close proximity to the wellhead. Other applications also exist topside, in which the operator would benefit from the installation of additional compression and processing capabilities at brown field facilities. Most of these existing installations have limited space for expansion and have strict size and weight limitations that have to be met by the additional equipment. This, in many cases, hinders the utilization of traditional compression and processing equipment, which is typically arranged using the large and heavy multi deck approach. A novel integrated compression system (ICS) has recently been developed to address the current need for compact compression systems that can handle wet process gas. The ICS makes use of centrifugal compressor stages driven directly by a high-speed, close-coupled electric motor, and incorporates a proprietary integrated centrifugal gas-liquid separation unit within the compressor case. This compact compression unit is packaged with process gas coolers in a single-lift module, providing a complete compression system that can be applied to all markets — upstream, midstream and downstream. With this integrated approach, the total footprint and weight of a conventional module or equipment layout can be greatly reduced. This paper is part of a series of publications that will describe the attributes of the new integrated compression system, and will serve to introduce the ICS and the benefits associated to the integration of the centrifugal separator into the compressor casing. The paper will focus on the OEM’s approach to Wet Gas Compression, with emphasis on the benefits of handling the liquid and vapor phases as separate streams, making the system more efficient and reliable than alternate solutions, including the ones that handle the wet gas directly. Finally the paper will provide a comparison between a traditional compression train and the new ICS to show how the latter system offers significant size and weight advantages.
A Low Affinity Cavb4a/Rem2 Interaction is Required for Inhibition of Cav2.1 Ca2+ Currents (2015)

RGK (Rem, Rad, Kir/Gem proteins) proteins, including Rem2, cause profound inhibition of high‐voltage activated Ca 2+ channels containing intracellular regulatory b subunits. All RGK proteins bind to Cavb subunits in vitro, but the necessity of the interaction for current inhibition remains controversial. This study applies solution state nuclear magnetic resonance (NMR) and calorimetric techniques to map the binding site for Rem2 on human Cavb4a and to measure the binding affinity. Our experiments revealed two binding surfaces on the b4 GK domain contributing to a 156 μM Kd interaction: 1) a hydrophobic pocket surrounded by four residues, mutation of any of which completely disrupted binding; and 2) a nearby surface containing three residues that when individually mutated decreased affinity. Cav2.1 Ca 2+ currents were completely inhibited by Rem2 when co‐expressed with wild‐type Cavb4a, but were unaffected by Rem2 when co‐expressed with a Cavb4a site 1 mutant. These results provide direct evidence for a low affinity Rem2/Cavb4 interaction and its essential role in Cav2.1 inhibition by Rem2.
Massive immune haemolysis after allogeneic peripheral blood stem cell transplantation with minor ABO incompatibility (2001)

Immune haemolysis as a result of minor ABO incompatibility is an underappreciated complication of haematopoietic transplantation. The increased lymphoid content of peripheral blood stem cell (PBSC) transplants may increase the incidence and severity of this event. We observed massive immune haemolysis in 3 out of 10 consecutive patients undergoing HLA‐identical, related‐donor PBSC transplants with minor ABO incompatibility. Non‐ablative conditioning had been given in 9 of these 10 cases, including two with haemolysis. Cyclosporin alone was used as prophylaxis against graft‐vs.‐host disease (GVHD). Catastrophic haemolysis of 78% of the circulating red cell mass led to anoxic death in the first case seen, but severe consequences were avoided by early, vigorous donor‐compatible red cell transfusions in the subsequent two cases. Haemolysis began 7–11 d after PBSC infusion and all patients with haemolysis had a positive direct antiglobulin test (DAT), with eluate reactivity against the relevant recipient antigen. However, neither the intensity of the DAT, the donor isohaemagglutinin titre, nor other factors could reliably be used to predict the occurrence of haemolysis. Our data indicate that haemolysis may be frequent and severe after transplantation of minor ABO‐incompatible PBSCs when utilizing cyclosporin alone to prevent GVHD. Meticulous clinical monitoring and early, vigorous donor‐compatible red cell transfusions should be practiced in all instances.
The Crystallization and Structure Analysis of Oligonucleotide Sequences (2003)

Until 1976, the study of nucleic acid structure was exclusively the domain of fiber diffractionists. Between the original Watson-Crick structure in 1953 and this date, there was considerable activity in refining the original B-form model of DNA and extending the approach to other polymorphs and a number of synthetic, repetitious polynucleotides, all of which were based on data from fiber-diffraction samples. These studies reached their zenith with the development and use of a "linked-atom," least-squares refinement procedure for the optimization of mono-or dinucleotide repeat units against the relatively sparse para-crystalline diffraction data from ordered fibers. It is a tribute to the sophistication of these analyses, in spite of the inherent limitations of fiber data, that the refined "canonical" A- and B-DNA double helices are still major reference pomts for many studies ().
General properties of two-dimensional conformal transformations in electrostatics (2011)

Electrostatic properties of two-dimensional nanosystems can be completely described by their non-trivial geometry modes. In this paper we prove that these modes as well as the corresponding eigenvalues are invariant under any conformal transformation. This invariance suggests a new way to study electrostatic conformal transformations, while also providing an in-depth interpretation of the behavior exhibited by singular plasmonic nanoparticles.
Phenotypic engineering by reprogramming gene transcription using novel artificial transcription factors in Escherichia coli (2008)

Now that many genomes have been sequenced and the products of newly identified genes have been annotated, the next goal is to engineer the desired phenotypes in organisms of interest. For the phenotypic engineering of microorganisms, we have developed novel artificial transcription factors (ATFs) capable of reprogramming innate gene expression circuits in Escherichia coli. These ATFs are composed of zinc finger (ZF) DNA-binding proteins, with distinct specificities, fused to an E. coli cyclic AMP receptor protein (CRP). By randomly assembling 40 different types of ZFs, we have constructed more than 6.4 x 10(4) ATFs that consist of 3 ZF DNA-binding domains and a CRP effector domain. Using these ATFs, we induced various phenotypic changes in E. coli and selected for industrially important traits, such as resistance to heat shock, osmotic pressure and cold shock. Genes associated with the heat-shock resistance phenotype were then characterized. These results and the general applicability of this platform clearly indicate that novel ATFs are powerful tools for the phenotypic engineering of microorganisms and can facilitate microbial functional genomic studies.
Selectively enhanced emission and suppression in Si0.5Ge0.5/Si multiple quantum wells by photonic crystals (2009)

Selective enhancement and suppression of the photoluminescence arising from Si0.5Ge0.5/Si multiple quantum wells by photonic crystals (PCs) have been demonstrated. The formation of the stop band in PCs is designed to be a filter as well as a reflector. It is found that the self-assembled PCs are able to selectively enhance the luminescence of the type-II transitions at the interface between Si and Si0.5Ge0.5/Si layers and suppress the emission from Si. Our working principle shown here can be extended to many other material systems and should be very useful for creating high power solid-state emitters.
Structure–Activity Relationships of C-17-Substituted Estratriene-3-O-sulfamates as Anticancer Agents (2011)

The synthesis and antiproliferative activities of analogues of 2-substituted estradiol-3,17-O,O-bis-sulfamates (E2bisMATEs) are discussed. Modifications of the C-17 substituent confirm that an H-bond acceptor is essential for high activity; its optimal linkage to C-17 and the local environment in which it resides are defined. In the non-sulfamoylated series 17β-acyl substitution delivers 48b, the most potent compound identified to date. In the sulfamate series a number of permutations of linker and H-bond acceptor deliver excellent activity, with 55, 61, 65, 49a, and 49b proving especially promising. The in vivo potential of these compounds was explored in the NCI hollow fiber assay and also in a mouse Matrigel model of antiangiogenesis in which 49 and 55 show significant inhibitory activity.
<title>Phase-matched second-harmonic generation in planar waveguides</title> (1993)

Using a planar, linear, waveguide second-harmonic generation was observed by nonlinear evanescent field interaction. In this class of devices phase-matching could be achieved with a periodically structured polymer adsorbate.
Modélisation et analyse numérique de couches limites réactives (1992)

These Ecole polytechnique federale de Lausanne EPFL, n° 1083 (1992) Reference doi:10.5075/epfl-thesis-1083Print copy in library catalog Record created on 2005-03-16, modified on 2016-08-08
Replication of diffractive-optical arrays via photocurable nanoimprint lithography (2006)

Photocurable nanoimprint lithography was used to replicate an array of Fresnel zone plates onto a SiO2 substrate. This array was transferred into the substrate and used for zone-plate-array lithography (ZPAL). The experimentally determined point-spread function showed good agreement with simulation. The authors also demonstrate the use of ZPAL as a tool for patterning and replicating diffractive optics.
Peroxisome proliferator-activated receptor α as a novel therapeutic target for schizophrenia (2020)

The findings of this study indicate that the mechanisms underlying schizophrenia pathogenesis involve PPARα-regulated transcriptional machinery and modulation of synapse physiology. Hence, PPARα can serve as a novel therapeutic target for schizophrenia.
Atorvastatin interferes with activation of human CD4+ T cells via inhibition of small guanosine triphosphatase (GTPase) activity and caspase-independent apoptosis (2006)

Although a beneficial effect of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, i.e. statins, on cell-mediated immunity has been suggested in vivo and in vitro, little is known about the molecular and biochemical events by which statins inhibit T cell proliferation. To address this question, we investigated the effects of atorvastatin (AT) on intracellular cytokine production, T cell activation markers, cell cycle progression and apoptosis in human CD4(+) T cells. AT did not influence intracellular cytokine production after short-term stimulation of whole blood with phorbol myristate acetate (PMA)/ionomycin or superantigen (SEB). In contrast, AT influenced CD45RA to RO switching dose-dependently, as well as CD25 expression, and caused cell cycle arrest in the G1 phase after long-term T cell stimulation. This occurred in conjunction with a reduced expression of cyclin-dependent kinases 2 and 4 and p21(wav1/cip1) and was paralleled by an increased protein expression of p27(kip1). In addition to G1 arrest, increased apoptosis was observed in AT-treated cells. In line with this, the expression of Bcl-xl and pBad were decreased by AT. Apoptosis was independent of caspases 3 and 9 activation. The inhibitory effect of AT on T cell proliferation could be overcome by addition of mevalonic acid or geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate or squalen, suggesting reduced protein prenylation. Activation of Rho, Rac and Ras were strongly reduced in AT-treated T cells, suggesting that impaired geranylation of these molecules might underlie the inhibitory effect of AT on T cell proliferation.
Low depth algorithms for quantum amplitude estimation (2020)

We design and analyze two new low depth algorithms for amplitude estimation (AE) achieving an optimal tradeoff between the quantum speedup and circuit depth. For $β\in (0,1]$, our algorithms require $N= \tilde{O}( \frac{1}{ ε^{1+β}})$ oracle calls and require the oracle to be called sequentially $D= O( \frac{1}{ ε^{1-β}})$ times to perform amplitude estimation within additive error $ε$. These algorithms interpolate between the classical algorithm $(β=1)$ and the standard quantum algorithm ($β=0$) and achieve a tradeoff $ND= O(1/ε^{2})$. These algorithms bring quantum speedups for Monte Carlo methods closer to realization, as they can provide speedups with shallower circuits. The first algorithm (Power law AE) uses power law schedules in the framework introduced by Suzuki et al \cite{S20}. The algorithm works for $β\in (0,1]$ and has provable correctness guarantees when the log-likelihood function satisfies regularity conditions required for the Bernstein Von-Mises theorem. The second algorithm (QoPrime AE) uses the Chinese remainder theorem for combining lower depth estimates to achieve higher accuracy. The algorithm works for discrete $β=q/k$ where $k \geq 2$ is the number of distinct coprime moduli used by the algorithm and $1 \leq q \leq k-1$, and has a fully rigorous correctness proof. We analyze both algorithms in the presence of depolarizing noise and provide numerical comparisons with the state of the art amplitude estimation algorithms.
Polymerization of α‐amino acid N‐carboxy anhydrides initiated by histamine in N,N‐dimethylformamide (1975)

Abstract The polymerization of α‐amino acid N ‐carboxy anhydrides (NCAs) initiated by 4‐aminoethylimidazole (histamine) was studied in order to synthesize poly(amino acids) containing an imidazole nucleus at the end of polymer chain. On the basis of the kinetical measurements, it was found that the rate of polymerization is proportional to the first order in both NCA and initiator concentrations and that the initiation reaction is predominantly caused by the primary amine with the highest basicity in a histamine molecule. Binding of the histamine fragment to the end of polymer chain was confirmed by elementary analysis, nuclear magnetic resonance spectroscopy, and measuring the number‐average molecular weight of the resulting polymers. It was thus possible to prepare poly(amino acids) with a pendant histamine. In addition, the lowering of the number‐average degree of polymerization of the polymers prepared was observed under the condition that the initial molar ratio of NCA to histamine was larger. It was caused by the reinitiation of polymerization by the imidazole nucleus at the chain end.