gebhart/patrepeval huggingface dataset:
A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization (2017)

Chimeric antigen receptors (CARs) can effectively redirect cytotoxic T cells toward highly expressed surface antigens on tumor cells. The low expression of several tumor-associated antigens (TAAs) on normal tissues, however, hinders their safe targeting by CAR T cells due to on-target/off-tumor effects. Using the multiple myeloma (MM)-associated CD38 antigen as a model system, here, we present a rational approach for effective and tumor-selective targeting of such TAAs. Using "light-chain exchange" technology, we combined the heavy chains of two high-affinity CD38 antibodies with 176 germline light chains and generated ∼124 new antibodies with 10- to >1,000-fold lower affinities to CD38. After categorizing them into three distinct affinity classes, we incorporated the single-chain variable fragments of eight antibodies from each class into new CARs. T cells carrying these CD38-CARs were extensively evaluated for their on-tumor/off-tumor cytotoxicity as well as CD38-dependent proliferation and cytokine production. We identified CD38-CAR T cells of ∼1,000- fold reduced affinity, which optimally proliferated, produced Th1-like cytokines, and effectively lysed CD38<sup>2+</sup> MM cells, but spared CD38<sup>+</sup> healthy hematopoietic cells in vitro and in vivo. Thus, this systematic approach is highly suitable for the generation of optimal CARs for effective and selective targeting of TAAs.
Expression, immobilization, and enzymatic characterization of cellulose-binding domain-organophosphorus hydrolase fusion enzymes (2000)

Bifunctional fusion proteins consisting of organophosphate hydrolase (OPH) moieties linked to a Clostridium-derived cellulose-binding domain (CBD) were shown to be highly effective in degrading organophosphate nerve agents, enabling purification and immobilization onto different cellulose materials in essentially a single step. Enzyme kinetics studies were performed for the CBD-OPH fusions using paraoxon as the substrate. The kinetics values of the unbound fusion enzymes were similar to OPH with a modest increase in K(m). Immobilization of the enzymes onto microcrystalline cellulose resulted in a further increase in the K(m) values of approximately twofold. The pH profile of the cellulose-immobilized enzymes was also only minimally affected. The CBD-OPH fusion proteins could be immobilized onto a variety of cellulose matrixes, and retained up to 85% of their original activity for 30 days. The durability of the bound fusions increased with the amount of Avicel used, suggesting that protein/cellulose interactions may have a dramatic stabilizing effect. Repeated hydrolysis of paraoxon was achieved in an immobilized enzyme reactor with 100% degradation efficiency over 45 days. These fusion proteins should prove to be invaluable tools for the development of low cost, OPH-based cellulose materials for the simultaneous adsorption and degradation of stored or spilled organophosphate wastes.
Object Distinction: Distinguishing Objects with Identical Names (2007)

Different people or objects may share identical names in the real world, which causes confusion in many applications. It is a nontrivial task to distinguish those objects, especially when there is only very limited information associated with each of them. In this paper, we develop a general object distinction methodology called DISTINCT, which combines two complementary measures for relational similarity: set resemblance of neighbor tuples and random walk probability, and uses SVM to weigh different types of linkages without manually labeled training data. Experiments show that DISTINCT can accurately distinguish different objects with identical names in real databases.
Dominant Negative Mutants of TRAF3 Reveal an Important Role for the Coiled Coil Domains in Cell Death Signaling by the Lymphotoxin-β Receptor (1997)

Ligation of the lymphotoxin-beta receptor (LTbetaR) recruits tumor necrosis factor receptor-associated factor-3 (TRAF3) and initiates cell death in HT29 adenocarcinoma cells. The minimal receptor binding domain (TRAF-C) defined by two hybrid analyses is not sufficient for direct recruitment to the ligated receptor. A series of TRAF3 deletion mutants reveal that a subregion of the coiled coil motif is required for efficient recruitment to the LTbetaR. Furthermore, the ability of TRAF3 to self-associate maps to an adjacent subregion. A TRAF3 deletion mutant that lacks the N-terminal zinc RING and zinc finger motifs, but retains the coiled coil and TRAF-C motifs, competitively displaces endogenous TRAF3 from the LTbetaR. A second TRAF3 mutant that lacks the receptor binding domain, yet contains the TRAF3 self-association domain, prevents TRAF3 homodimers from being recruited to the LTbetaR. Both of these mutants have a dominant negative effect on cell death and demonstrate that the recruitment of TRAF3 oligomers is necessary to initiate signal transduction that activates the cell death pathway.
Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and epo to stimulate human progenitor cells of the myeloid and erythroid lineages. (1991)

The cDNA for human stem cell factor (hSCF) has been cloned and expressed in mammalian and bacterial hosts and recombinant protein purified. We have examined the stimulatory effect of recombinant human SCF (rhSCF) on human bone marrow cells alone and in combination with recombinant human colony stimulating factors (CSFs) and erythropoietin (rhEpo). RhSCF alone resulted in no significant colony formation, however, in the presence of rhGM-CSF, rhG-CSF or rhIL-3, rhSCF stimulated a synergistic increase in colony numbers. In addition, increased colony size was stimulated by all combinations. The morphology of cells in the colonies obtained with the CSFs plus rhSCF was identical to the morphology obtained with rhGM-CSF, rhG-CSF or rhIL-3 alone. RhEpo also synergised with rhSCF to stimulate the formation of large compact hemoglobinized colonies which stained positive for spectrin and transferrin receptor and had a morphological appearance consistent with normoblasts. RhSCF stimulation of low density non-adherent, antibody depleted, CD34+ cells suggests that rhSCF directly stimulates progenitor cells capable of myeloid and erythroid differentiation.
Mechanisms and Signals for the Nuclear Import of Proteins (2009)

In eukaryotes, the nuclear membrane provides a physical barrier to the passive diffusion of macromolecules from and into the cytoplasm. Nucleocytoplasmic traffic occurs through highly specialized structures known as nuclear pores, and involves the participation of a special class of transport proteins. Active transport across the nuclear pores is an energy-dependent process that relies on the activity of Ran-GTPases both in the nuclear and cytoplasmic compartments. Nuclear import of proteins is an essential step in regulating gene expression and the replication cycle of several viruses. In this review, the key mechanisms, pathways, and models underlying the transport of proteins across nuclear pores are analysed.
Barren plateaus in quantum neural network training landscapes (2018)

Many experimental proposals for noisy intermediate scale quantum devices involve training a parameterized quantum circuit with a classical optimization loop. Such hybrid quantum-classical algorithms are popular for applications in quantum simulation, optimization, and machine learning. Due to its simplicity and hardware efficiency, random circuits are often proposed as initial guesses for exploring the space of quantum states. We show that the exponential dimension of Hilbert space and the gradient estimation complexity make this choice unsuitable for hybrid quantum-classical algorithms run on more than a few qubits. Specifically, we show that for a wide class of reasonable parameterized quantum circuits, the probability that the gradient along any reasonable direction is non-zero to some fixed precision is exponentially small as a function of the number of qubits. We argue that this is related to the 2-design characteristic of random circuits, and that solutions to this problem must be studied.
Hypoxia induces type II NOS gene expression in pulmonary artery endothelial cells via HIF-1 (1998)

Type II nitric oxide synthase (NOS) is upregulated in the pulmonary vasculature in a chronic hypoxia model of pulmonary hypertension. In situ hybridization analysis demonstrates that type II NOS RNA is increased in the endothelium as well as in the vascular smooth muscle in the lung. The current studies examine the role of hypoxia-inducible factor (HIF)-1 in regulating type II NOS gene expression in response to hypoxia in pulmonary artery endothelial cells. Northern blot analyses demonstrate a two fold increase in HIF-1 alpha but not in HIF-1 beta RNA with hypoxia in vivo and in vitro. Electrophoretic mobility shift assays show the induction of specific DNA binding activity when endothelial cells were subjected to hypoxia. This DNA binding complex was identified as HIF-1 using antibodies directed against HIF-1 alpha and HIF-1 beta. Transient transfection of endothelial cells resulted in a 2.7-fold increase in type II NOS promoter activity in response to hypoxia compared with nonhypoxic controls. Mutation or deletion of the HIF-1 site eliminated the response to hypoxia. These results demonstrate that HIF-1 is essential for the hypoxic regulation of type II NOS gene transcription in pulmonary endothelium.
Integrated acoustooptic circuits and applications (1992)

The recent development of titanium-indiffusion proton-exchange (TIPE) microlenses and lens arrays has made possible the construction of a variety of single- and multichannel integrated acoustooptic (AO) and acoustooptic-electrooptic (EO) circuits in LiNbO(3) channel-planar waveguides 0.1x1.0x2.0 cm(3) in size. These hybrid AO and AO-EO circuits can be fabricated through compatible and well-established technologies. The most recent realization of ion-milled microlenses and lens arrays together with the recent development of gigahertz AO Bragg modulators and EO Bragg modulator arrays have also paved the way for construction of similar but monolithic AO and AO-EO GaAs/GaAlAs waveguides of comparable size. Both types of integrated AO and AO-EO circuits suggest versatile applications in communications signal processing, and computing. Efficient and simultaneous excitation of the channel waveguide array using an ion-milled planar microlens array has facilitated the demonstration of some of these applications.
Resonance effects in broadband acoustic cloak with multilayered homogeneous isotropic materials (2008)

The frequency response of the multilayered acoustic cloak made of isotropic materials is analyzed by the acoustic scattering theory. When concealing a rigid cylinder, the acoustic total scattering cross section (TSCS) monotonically increases with frequency. If concealing penetrable materials, the cloak-induced reverse-phase monopole and dipole resonances can increase the TSCS around the resonant frequencies, while the in-phase monopole resonance decreases the TSCS. The results are confirmed by numerical simulations of the finite element method.
Soil water flux density measurements near 1 cm d−1 using an improved heat pulse probe design (2008)

The heat pulse probe (HPP) technique has been successfully applied for estimating water flux density (WFD). Estimates of WFD have been limited to values greater than 10 cm d −1 , except for two recent studies with lower detection limits of 2.4 and 5.6 cm d −1 . Although satisfactory for saturated soils, it is recognized that current HPP capabilities are limited for applications in the vadose zone, where WFD values are generally below 1 cm d −1 . Since numerical sensitivity analysis has shown that large heater needle diameters may increase HPP capabilities in the lower flux density range, a HPP with a 4‐mm‐diameter heater needle was developed and tested. WFD values were obtained by fitting temperature data to the analytical solution for a pulsed cylindrical heat source of infinite length. Effective heater‐thermistor distance and soil thermal diffusivity values were determined for specific heat input scenarios with zero WFD, prior to imposing water flow across the HPP needles. We showed excellent results in the range of 1–10 cm d −1 and satisfactory results in the range of 10–1000 cm d −1 .
Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila (1992)

hedgehog is a segment polarity gene necessary to maintain the proper organization of each segment of the Drosophila embryo. We have identified the physical location of a number of rearrangement breakpoints associated with hedgehog mutations. The corresponding hh RNA is expressed in a series of segmental stripes starting at cellular blastoderm in the posterior portion of each segment. This RNA is localized predominantly within nuclei until stage 10, when the localization becomes primarily cytoplasmic. Expression of hh RNA in the posterior compartment is independent of most other segment polarity genes, including en, until the late extended germ-band stage (stage 11). Sequence analysis of the hedgehog locus suggests the protein product is a transmembrane protein, which may, therefore, be directly involved in cell-cell communication.
ChemInform Abstract: Construction of the (1α,5α,6α)‐6‐Amino‐3‐azabicyclo( 3.1.0)hexane Ring System. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Amino acid ingestion and glucose metabolism—A review (2010)

Interest in the effect of proteins or amino acids on glucose metabolism dates back at least a century, largely because it was demonstrated that the amino acids from ingested protein could be converted into glucose. Indeed, these observations influenced the dietary information provided to people with diabetes. Subsequently it was shown that ingested protein did not raise the blood glucose concentration. It also was shown that proteins could stimulate a rise in insulin and glucagon but the response to various proteins was different. In addition, it was shown that individual amino acids also could stimulate a rise in insulin and in glucagon concentrations. When individual amino acids are ingested by normal subjects, there is an ordering of the insulin and glucagon responses. However, the order is not the same for insulin and glucagon. In addition, the metabolic response cannot be predicted based on the functional groups of the amino acids. Thus, empirical prediction of the metabolic response to ingested single amino acids is not possible.
[The remineralization of enamel lesions by casein phosphopeptide-amorphous calcium fluoride phosphate in vitro]. (2001)

The 2% CPP-ACFP solution could significantly remineralize the artificial enamel subsurface lesion in vitro. The remineralizing rates were increased with the experiment time (within 10 days).
Post-translational Modifications and Their Biological Functions: Proteomic Analysis and Systematic Approaches (2004)

Recently produced information on post-translational modifications makes it possible to interpret their biological regulation with new insights. Various protein modifications finely tune the cellular functions of each protein. Understanding the relationship between post-translational modifications and functional changes ("post-translatomics") is another enormous project, not unlike the human genome project. Proteomics, combined with separation technology and mass spectrometry, makes it possible to dissect and characterize the individual parts of post-translational modifications and provide a systemic analysis. Systemic analysis of post-translational modifications in various signaling pathways has been applied to illustrate the kinetics of modifications. Availability will advance new technologies that improve sensitivity and peptide coverage. The progress of "post-translatomics", novel analytical technologies that are rapidly emerging, offer a great potential for determining the details of the modification sites.
Deposition of plasma fibronectin in tissues. (1981)

Tissue distribution of human fibronectin injected intravenously into mice was studied by using immunofluorescence with species-specific antisera to human and mouse fibronectins. Human fibronectin was detected in the tissues of mice injected with human fibronectin. The distribution of the injected fibronectin was indistinguishable from that of mouse fibronectin. The staining for human fibronectin in the livers of injected mice was unaffected by perfusion of the livers prior to the preparation of tissue sections, and human IgG injected in mice as a control was not detectable in tissues by immunofluorescence. Mice were also injected with fragments of fibronectin with molecular weights close to 200,000. These fragments lack parts of the NH2 and COOH termini of the fibronectin polypeptide, including the part with the interchain disulfide bond(s), but retain the ability to bind to collagen and heparin and the ability to mediate cell attachment. They showed essentially no tissue incorporation, suggesting that the integrity of the fibronectin molecule is important for the accumulation of fibronectin in tissues. The incorporation of injected fibronectin into tissues demonstrated here suggests that circulating fibronectin contributes to the extracellular matrix of tissues.
SERS‐Coded Gold Nanorods as a Multifunctional Platform for Densely Multiplexed Near‐Infrared Imaging and Photothermal Heating (2009)

Screening nanorods coated with a mixture of SERS active molecules and biocompatible polymer identifies three formulations that may be uniquely distinguished in vivo over a spectral bandwidth of only 6 nm in the near-infrared (a spectral multiplexing density over an order of magnitude greater than attainable with semiconductor quantum dots, organic fluorochromes, and Raleigh scattering nanoparticle imaging approaches), while providing intense photothermal heating for cancer therapy.
Candidate's Thesis: Direct Evidence of Bacterial Biofilms in Otitis Media (2001)

Bacterial biofilms form on the middle-ear mucosa of chinchillas in experimentally induced H. influenzae otitis media and can form on tympanostomy tubes placed in children's ears. Such biofilms can be directly observed by microscopy. These results reinforce the hypothesis that the bacterial aggregates called biofilms, resistant to treatment by antibiotics and to detection by standard culture techniques, may play a major etiologic role in OME and in one of its frequent complications, post-tympanostomy otorrhea.
Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. (1990)

We have used restriction isotyping (restriction enzyme isoform genotyping) for rapid typing of common apolipoprotein E isoforms (E2, E3, E4). ApoE restriction isotyping used oligonucleotides to amplify apolipoprotein E gene sequences containing amino acid positions 112 and 158. The amplification products were digested with HhaI and subjected to electrophoresis on polyacrylamide gels. Each of the isoforms was distinguished by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations. HhaI cleaves at GCGC encoding 112arg (E4) and 158arg (E3, E4), but does not cut at GTGC encoding 112cys (E2, E3) and 158cys (E2).
(Zn,Cd)Se/ZnSe quantum-well lasers: Excitonic gain in an inhomogeneously broadened quasi-two-dimensional system (1993)

Optical properties of a strongly excitonic quasi-two-dimensional system in a wide-band-gap II-VI semiconductor heterostructure are investigated in terms of the relationship between absorption and stimulated emission. In particular, the optical gain in (Zn,Cd)Se/ZnSe quantum-well lasers is demonstrated to be of excitonic nature over a wide range of temperatures, and to occur at electron-hole pair densities below the exciton-electron hole plasma transition. Both steady-state and transient (picosecond and femtosecond) spectroscopic techniques have been applied to detail exciton kinetics within the n=1 heavy-hole exciton resonance. A phenomenological model of optical gain is proposed, originating from an inhomogeneously broadened exciton resonance and including the effects of exciton-phonon interaction.
"If Property Rights Were Treated Like Human Rights, They Could Never Get away with This": Blacklisting and Due Process in U.S. Economic Sanctions Programs (1999)

Economic sanctions have proliferated in the last half of the twentieth century, and become the "first choice" of policymakers seeking tools to address many complex international issues. A key feature of these various sanctions programs is the use of a blacklist, to bring third party agents, controlled entities, and corporate cloaks operating elsewhere within the ambit of the sanctions aimed at a particular country or destination. These blacklists have now grown to include several thousand individuals and entities. However, despite the growing importance of economic sanctions, and their accompanying blacklists, these programs are still managed by a relatively small office within the Treasury Department, the Office of Foreign Assets Control (OFAC).\nUsing the example of the IPT Company, Inc., a small but long established U.S. based corporation with foreign ownership, and the economic sanctions program targeted at the Federal Republic of Yugoslavia, this Article examines the processes used by OFAC to establish, impose, and implement such sanctions on a particular destination, and the closely related process of blacklisting particular parties associated with the sanctioned destination. It explores the unique, adversarial, relationship with the public which characterized much of OFAC's operations until recent years, and the impact that attitude has had on the promulgation, notice, distribution, and enforcement of OFAC's regulations. After considering the important, but limited, role individual case by case challenges have played in improving these processes, the Article concludes by suggesting that new legislation is required to remedy ongoing deficiencies in OFAC's implementation of its programs. Accordingly, Professor Fitzgerald urges that the pending Sanctions Reform Act be expanded to provide detailed guidance on how sanctions should be implemented, in a manner similar to the way the U.S. Congress has both directed and overseen the operation of the export control system with the Export Administration Act.