gebhart/patrepeval huggingface dataset:
Targeting IFNα to tumor by anti-PD-L1 creates feedforward antitumor responses to overcome checkpoint blockade resistance (2018)

Many patients remain unresponsive to intensive PD-1/PD-L1 blockade therapy despite the presence of tumor-infiltrating lymphocytes. We propose that impaired innate sensing might limit the complete activation of tumor-specific T cells after PD-1/PD-L1 blockade. Local delivery of type I interferons (IFNs) restores antigen presentation, but upregulates PD-L1, dampening subsequent T-cell activation. Therefore, we armed anti-PD-L1 antibody with IFNα (IFNα-anti-PD-L1) to create feedforward responses. Here, we find that a synergistic effect is achieved to overcome both type I IFN and checkpoint blockade therapy resistance with the least side effects in advanced tumors. Intriguingly, PD-L1 expressed in either tumor cells or tumor-associated host cells is sufficient for fusion protein targeting. IFNα-anti-PD-L1 activates IFNAR signaling in host cells, but not in tumor cells to initiate T-cell reactivation. Our data suggest that a next-generation PD-L1 antibody armed with IFNα improves tumor targeting and antigen presentation, while countering innate or T-cell-driven PD-L1 upregulation within tumor.
Sequence analysis and bacterial production of the anti‐c‐myc antibody 9E10: the VH domain has an extended CDR‐H3 and exhibits unusual solubility (1997)

The cDNAs for the two variable domains of the antibody 9E10 were cloned from the hybridoma cell line. A chimeric 9E10 Fab fragment was produced in E. coli under control of the tightly controlled tetracycline promoter. The functional Fab fragment was isolated in a single step via a His6-tag, which also served for its recognition by a nickel chelate-alkaline phosphatase conjugate. Thus, the recombinant Fab fragment permitted the immunochemical detection of the myc tag in a sandwich ELISA. The dissociation constant for the interaction with the myc tag peptide was determined as 80 +/- 5 nM by fluorescence titration. In an attempt to produce the smaller 9E10 Fv fragment it was found that its V(H) domain alone can be readily isolated from E. coli as a soluble protein. This unusual behaviour may be explained by the 18 amino acid-long CDR-H3 and could be of value in the design of 'single domain' antibodies.
Chemical synthesis of biologically active oligoribonucleotides using β-cyanoethyl protected ribonucleoside phosphoramidites (1990)

The preparation of fully protected diisopropylamino-beta-cyanoethyl ribonucleoside phosphoramidites with regioisomeric purity greater than 99.95% is described. It is demonstrated that the combination of standard DNA protecting groups, 5'-O-DMT, N-Bz (Ade and Cyt), N-iBu (Gua), beta-cyanoethyl for phosphate, in conjunction with TBDMS for 2'-hydroxyl protection, constitutes a reliable method for the preparation of fully active RNA. Average stepwise coupling yields in excess of 99% were achieved with these synthons on standard DNA synthesizers. Two steps completely deprotect the oligoribonucleotide and workup is reduced to a fifteen minute procedure. Further, it is shown that the deprotected oligoribonucleotides are free from 5'-2' linkages. This methodology was applied to the chemical synthesis of a 24-mer microhelix, a 35-mer minihelix and two halves of a catalytic 'Hammerhead Ribozyme'. These oligoribonucleotides were directly compared in two distinct biochemical assays with enzymatically (T7 RNA polymerase) prepared oligoribonucleotides and shown to possess equal or better activity.
Progressive Multifocal Leukoencephalopathy (PML) Development Is Associated With Mutations in JC Virus Capsid Protein VP1 That Change Its Receptor Specificity (2011)

Progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease caused by JC virus (JCV) infection of oligodendrocytes, may develop in patients with immune disorders following reactivation of chronic benign infection. Mutations of JCV capsid viral protein 1 (VP1), the capsid protein involved in binding to sialic acid cell receptors, might favor PML onset. Cerebrospinal fluid sequences from 37/40 PML patients contained one of several JCV VP1 amino acid mutations, which were also present in paired plasma but not urine sequences despite the same viral genetic background. VP1-derived virus-like particles (VLPs) carrying these mutations lost hemagglutination ability, showed different ganglioside specificity, and abolished binding to different peripheral cell types compared with wild-type VLPs. However, mutants still bound brain-derived cells, and binding was not affected by sialic acid removal by neuraminidase. JCV VP1 substitutions are acquired intrapatient and might favor JCV brain invasion through abrogation of sialic acid binding with peripheral cells, while maintaining sialic acid-independent binding with brain cells.
Giant Magnetocaloric Effect inGd5(Si2Ge2) (1997)

An extremely large magnetic entropy change has been discovered in $\mathrm{Gd}{}_{5}(\mathrm{Si}{}_{2}\mathrm{Ge}{}_{2})$ when subjected to a change in the magnetic field. It exceeds the reversible (with respect to an alternating magnetic field) magnetocaloric effect in any known magnetic material by at least a factor of 2, and it is due to a first order $[\mathrm{ferromagnetic}(\mathrm{I})\ensuremath{\leftrightarrow}\mathrm{ferromagnetic}(\mathrm{II})]$ phase transition at 276 K and its unique magnetic field dependence.
Expansion Microscopy: Protocols for Imaging Proteins and RNA in Cells and Tissues (2018)

Expansion microscopy (ExM) is a recently developed technique that enables nanoscale-resolution imaging of preserved cells and tissues on conventional diffraction-limited microscopes via isotropic physical expansion of the specimens before imaging. In ExM, biomolecules and/or fluorescent labels in the specimen are linked to a dense, expandable polymer matrix synthesized evenly throughout the specimen, which undergoes 3-dimensional expansion by ∼4.5 fold linearly when immersed in water. Since our first report, versions of ExM optimized for visualization of proteins, RNA, and other biomolecules have emerged. Here we describe best-practice, step-by-step ExM protocols for performing analysis of proteins (protein retention ExM, or proExM) as well as RNAs (expansion fluorescence in situ hybridization, or ExFISH), using chemicals and hardware found in a typical biology lab. Furthermore, a detailed protocol for handling and mounting expanded samples and for imaging them with confocal and light-sheet microscopes is provided. © 2018 by John Wiley & Sons, Inc.
High-sweep-rate 1310 nm MEMS-VCSEL with 150 nm continuous tuning range (2012)

Microelectromechanical-systems-based vertical-cavity surface-emitting lasers (MEMS-VCSELs) capable of a 150 nm continuous tuning range near 1310 nm are demonstrated. These devices employ a thin optically pumped active region structure with large free-spectral range, which promotes wide and continuous tuning. To achieve VCSEL emission at 1310 nm, a wide-gain-bandwidth indium phosphide-based multiple quantum well active region is combined with a wide-bandwidth fully oxidised GaAs-based mirror through wafer bonding, with tuning enabled by a suspended dielectric top mirror. These devices are capable of being scanned over the entire tuning range at frequencies up to 500 kHz, making them ideal for applications such as swept source optical coherence tomography and high-speed transient spectroscopy.
Enzymatic excision from γ-irradiated polydeoxyribonucleotids of adenine residues whose imidazole rings have been rypture (1984)

The main forms of base damage in polydeoxyadenylic acid gamma-irradiated under hypoxic conditions are due to saturation and fragmentation of the adenine imidazole ring. An irradiated polymer was annealed with an equimolar amount of poly (dT) to generate a double-stranded polydeoxyribonucleotide containing scattered damaged base residues. On incubation of the latter with partially purified cell extracts of E.coli, imidazole ring-opened adenine, i.e. 4,6-diamino-5-formamidopyrimidine, was released in free form by a DNA glycosylase activity. The enzyme has been purified 4,500-fold, has Mr = 29,000, and appears to be identical with the previously described DNA repair enzyme formamidopyrimidine-DNA glycosylase.
Mouse Myeloma Cell Line Secreting Bifunctional Fusion Protein RM4/IFN-τ Elicits Antitumor CD8 MHC Class I-Restricted T Cells That Are Cytolytic In Vitro and Tumoricidal In Vivo (1996)

Mouse myeloma cell line VKCK/RM4-IFN-gamma secreting the bifunctional fusion protein RM4/IFN-gamma was used to study the relationship between IFN-gamma secretion of tumor cells and its tumorigenicity and to study the potential mechanism responsible for the immune response. IFN-gamma secretion of VKCK/RM4-IFN-gamma tumor cells was estimated at 90 U/ml using an antiviral assay. To evaluate tumorigenicity, 5 x 10(5) viable IFN-gamma-secreting VKCK/RM4-IFN-gamma and non-IFN-gamma-secreting VKCK tumor cells were injected s.c. into syngeneic BALB/c mice and VKCK/RM4-IFN-gamma-immunized or T cell subset-depleted BALB/c mice, respectively. Tumor progression or regression was evaluated 2 weeks after tumor inoculation. Our animal studies showed that RM4/IFN-gamma secretion by VKCK/RM4-IFN-gamma tumor cells curtailed its tumorigenicity in BALB/c mice and induced a persistant protective immune response against a subsequent graft of parental VKCK tumor. This protective immunity is long term and tumor specific as measured in a 51Cr-release assay. In addition, our animal studies in T cell subset-depleted BALB/c mice showed that CD8 CTL play a major role in the reduction of tumorigenicity. This study thus highlights the potential advantages of localized IFN-gamma in tumors to induce potent antitumor immunity and further suggests that the bifunctional fusion protein RM4/IFN-gamma may be useful in cancer immunotherapy because of its capacity of targeting IFN-gamma to human tumors expressing the human tumor-associated TAG72 antigen [corrected].
Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. (1983)

Recent studies suggested that the clonally unique Ti epitopes defined by non-cross-reactive monoclonal antibodies might represent the variable regions of the antigen receptor. Here we determine whether such anti-Ti antibodies could trigger clonal T cell activation. Anticlonotypic monoclonal antibodies to the 49/43-kdalton heterodimer of a given clone or antibodies to the 20/25-kdalton membrane associated monomorphic T3 molecule selectively induce proliferation and IL-2 secretion when linked to a solid support. In contrast, anti-T4 and anti-T8 antibodies under the same conditions have no effect. In conclusion, these results imply that anticlonotypic antibody functions in a fashion analogous to antigen and further support the notion that the T3-Ti molecular complex represents the antigen receptor on human T lymphocytes.
T helper subset development: roles of instruction, selection, and transcription (2002)

The past 15 years have seen the development of a field in immunology entirely devoted to understanding the divergence of CD4+ T cells into distinct cytokine-producing subsets. Generally speaking, the immune response to a pathogen can develop toward a more strongly cellular type (type 1), or toward a more allergic type of response (type 2). When well developed, these gear the immune response for the effective elimination of different types of pathogens, with a type 1 response being more effective against intracellular pathogens, for example Listeria monocytogenes or mycobacteria. Type 2 allergic responses, in contrast, favor the elimination of parasites such as helminths. The basis for this selective action resides in the cytokines made by the CD4+ T helper cell subsets in these responses. T helper type 1 (Th1) cells produce several characteristic cytokines, most notably IL-2 and IFN-γ, whereas Th2 cells produce a set of cytokines, most notably IL-4, IL-5, and IL-13. In turn, IL-2 and IFN-γ promote the development of strong cell-mediated immunity, whereas the type 2 cytokines promote allergic responses effective in eliminating parasites.

When confronted with a pathogen, it is important that the immune system activate the appropriate type of response. Fortunately, it has developed reliable mechanisms that help naive CD4 T cells in this choice. These mechanisms have been fairly well worked out at many levels over the last decade, and several thorough reviews have described recent findings regarding the signaling pathways and transcription factors that contribute to peripheral CD4+ Th development (1–3).

Despite the great progress in the molecular understanding of these processes, there are still issues in this area that are controversial and actively debated. Here, we will focus on some aspects that are unresolved within the various models of Th1 and Th2 development and will try to fit together some of the recent observations that have motivated these somewhat theoretical considerations. In particular, we will take this opportunity to focus on a difficult topic, that of whether Th1/Th2 development rests on selective or instructive mechanisms, a general issue that is also debated in regard to CD4/CD8 lineage commitment and is common to many developmental systems. Distinguishing between strictly selective and instructive models is difficult, as many experimental results can be compatible with both interpretations.
A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral Nerves (2018)

A wireless electrical stimulation implant for peripheral nerves, achieving >10× improvement over state of the art in the depth/volume figure of merit, is presented. The fully integrated implant measures just 2 mm × 3 mm × 6.5 mm (39 mm<sup>3</sup>, 78 mg), and operates at a large depth of 10.5 cm in a tissue phantom. The implant is powered using ultrasound and includes a miniaturized piezoelectric receiver (piezo), an IC designed in 180 nm HV BCD process, an off-chip energy storage capacitor, and platinum stimulation electrodes. The package also includes an optional blue light-emitting diode for potential applications in optogenetic stimulation in the future. A system-level design strategy for complete operation of the implant during the charging transient of the storage capacitor, as well as a unique downlink command/data transfer protocol, is presented. The implant enables externally programmable current-controlled stimulation of peripheral nerves, with a wide range of stimulation parameters, both for electrical (22 to 5000 μA amplitude, ∼14 to 470 μs pulse-width, 0 to 60 Hz repetition rate) and optical (up to 23 mW/mm<sup>2</sup> optical intensity) stimulation. Additionally, the implant achieves 15 V compliance voltage for chronic applications. Full integration of the implant components, end-to-end in vitro system characterizations, and results for the electrical stimulation of a sciatic nerve, demonstrate the feasibility and efficacy of the proposed stimulator for peripheral nerves.
On the Optimal Speed Profile for Eco-Driving on Curved Roads (2018)

The horizontal curvature and a driver’s behavior on curved roads significantly affect vehicle fuel economy. This paper describes how optimal speed profiles can minimize fuel consumption for a vehicle travelling on a curve. Previous studies suggested that sustaining a constant speed throughout a level road is the optimal measure for conserving fuel, within certain bounds. Based on the established vehicle dynamic model and an instantaneous fuel consumption model, the optimal constant speeds corresponding to circular curves with different radii can be derived. When entering or departing a curve for additional study, a dynamic programming algorithm is tailored to obtain the optimal speed profile in the vicinity of the curve. The algorithm is verified by using co-simulation of CarSim and Matlab/Simulink, and the results show the algorithm can save approximately 5.46% to 17.64% of fuel compared with the deceleration and acceleration modes of typical driver model controlled by a proportional integral controller. This technology can not only improve the conventional vehicle fuel economy by taking into account the horizontal curvature but also provide decision-making reference for the autonomous vehicle speed control.
Structures and functions of the sugar chains of glycoproteins (1992)

Most proteins within living organisms contain sugar chains. Recent advancements in cell biology have revealed that many of these sugar chains play important roles as signals for cell-surface recognition phenomena in multi-cellular organisms. In order to elucidate the biological information included in the sugar chains and link them with biology, a novel scientific field called 'glycobiology' has been established. This review will give an outline of the analytical techniques for the structural study of the sugar chains of glycoproteins, the structural characteristics of the sugar chains and the biosynthetic mechanism to produce such characteristics. Based on this knowledge, functional aspects of the sugar chains of glycohormones and of those in the immune system will be described to help others understand this new scientific field.
Structural properties of undoped and doped cubic GaN grown on SiC(001) (2002)

Transmission electron microscopy and x-ray diffraction measurements reveal the presence of stacking faults (SFs) in undoped cubic GaN thin layers. We demonstrate the importance of the defects in the interfacial region of the films by showing that the SFs act as nucleation sites for precipitates of residual impurities such as C and Si present in the GaN layers grown on SiC(001) substrates. We used the imaging secondary ion mass spectroscopy technique to locate these impurities. The systematic decrease of the SF density as a function of the layer thickness is explained by an annihilation mechanism. Finally, the effects of usual dopants on the structural properties of GaN layers are discussed. It is shown that Mg has a tendency to incorporate out of the Ga site by forming Mg precipitates for a concentration higher than 1019 cm−3 in contrast with the results found for heavily Si doped layers.
Generalized spectral bounds for sparse LDA (2006)

We present a discrete spectral framework for the sparse or cardinality-constrained solution of a generalized Rayleigh quotient. This NP-hard combinatorial optimization problem is central to supervised learning tasks such as sparse LDA, feature selection and relevance ranking for classification. We derive a new generalized form of the Inclusion Principle for variational eigenvalue bounds, leading to exact and optimal sparse linear discriminants using branch-and-bound search. An efficient greedy (approximate) technique is also presented. The generalization performance of our sparse LDA algorithms is demonstrated with real-world UCI ML benchmarks and compared to a leading SVM-based gene selection algorithm for cancer classification.
Loading Strategies in Acute Mania (2001)

Treatment of acute mania has been greatly influenced by loading strategies. Loading has potential benefits, including rapid symptom reduction in mania and a shortened length of stay. Disadvantages include an increased likelihood of adverse effects of the medications. Loading strategies for lithium, valproic acid (divalproex sodium), carbamazepine, oxcarbazepine, olanzapine, and haloperidol decanoate in the treatment of acute mania are discussed. Recent studies highlight this treatment option for selected patients. It is the unique properties of the medications that influence their use in loading. Issues in patient selection for loading strategies with each medication are also considered.
Centimeter‐Long V2O5 Nanowires: From Synthesis to Field‐Emission, Electrochemical, Electrical Transport, and Photoconductive Properties (2010)

High-quality single-crystalline centimeter-long V2O5 nanowires are produced using an environmental friendly hydrothermal approach without dangerous reagents or harmful solvents and surfactants. The field-emission, electrochemical, and electrical transport, and photoconductive properties are thoroughly investigated and suggest a high potential of utilizing these novel nanowires in field emitters, lithium ion batteries, interconnects, and optoelectronic devices. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Superstructures of self-assembled cobalt nanocrystals (2004)

Uniform three-dimensional superstructures of spherical cobalt nanocrystals are produced by the interplay between dipolar interaction and applied magnetic field. An anomalous low-temperature magnetic behavior is observed, indicating that uncompensated surface spins become ordered below 10 K, as evidenced by the presence of two magnetic phases that superimpose in hysteresis loops as compared to measurements at 20 K. The approach discussed here provides a framework for applications such as high-performance mesomagnets, microelectronic and magnetic devices fabrication, and can be extended to other nanocomposite materials fabrication if cobalt particles can act as carriers for other nanoparticles.
Platelet adhesion to novel phospholipid materials: Modified phosphatidylcholine covalently immobilized to silica, polypropylene, and PTFE materials (1996)

Based on the premise of achieving blood compatibility through mimicking the chemical constitutents of the biologically insert surface of the unactivated platelet membrane, a process was developed that entails the covalent grafting of modified phosphatidylcholine molecules to materials including silica, polypropylene, and polytetrafluoroethylene (PTFE) polymer films. These materials were characterized using x-ray photoelectron spectroscopy (XPS) and contactangle measurements. The phosphatidylcholine-containing materials (PC materials) were used as substrates in the plateletadhesion assays and were subjected to enzymatic degradation evaluation. Phosphatidylcholine-grafted silica materials do not support platelet adhesion. In addition the number of adherent platelets correlate with the amount of grafted phospholipid present, as indicated by the phosphorus/ carbon ratio obtained by XPS analysis. Platelet adhesion to phosphatidylcholine-grafted polypropylene and PTFE was inhibited 80% and 90%, respectively, when compared with platelet adhesion to unmodified polypropylene and PTFE.
Theoretical Basis of Bouguer-Beer Law of Radiation Absorption (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTheoretical Basis of Bouguer-Beer Law of Radiation AbsorptionF. C. StrongCite this: Anal. Chem. 1952, 24, 2, 338–342Publication Date (Print):February 18, 1952Publication History Published online1 May 2002Published inissue 18 February 1952https://pubs.acs.org/doi/10.1021/ac60062a020https://doi.org/10.1021/ac60062a020research-articleACS PublicationsRequest reuse permissionsArticle Views931Altmetric-Citations39LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts