gebhart/patrepeval huggingface dataset:
The Domains of Glycoprotein D Required To Block Apoptosis Induced by Herpes Simplex Virus 1 Are Largely Distinct from Those Involved in Cell-Cell Fusion and Binding to Nectin1 (2003)

Glycoprotein D (gD) interacts with two alternative protein receptors, nectin1 and HveA, to mediate herpes simplex virus (HSV) entry into cells. Fusion of the envelope with the plasma membrane requires, in addition to gD, glycoproteins gB, gH, and gL. Coexpression of the four glycoproteins (gD, gB, gH, and gL) promotes cell-cell fusion. gD delivered in trans is also capable of blocking the apoptosis induced by gD deletion viruses grown either in noncomplementing cells (gD(-/-)) or in complementing cells (gD(-/+)). While ectopic expression of cation-independent mannose-6 phosphate receptor blocks apoptosis induced by both stocks, other requirements differ. Thus, apoptosis induced by gD(-/-) virus is blocked by full-length gD (or two gD fragments reconstituting a full-length molecule), whereas ectopic expression of the gD ectodomain is sufficient to block apoptosis induced by gD(-/+) virus. In this report we took advantage of a set of gD insertion-deletion mutants to map the domains of gD required to block apoptosis by gD(-/-) and gD(-/+) viruses and those involved in cell-cell fusion. The mutations that resulted in failure to block apoptosis were the same for gD(-/-) and gD(-/+) viruses and were located in three sites, one within the immunoglobulin-type core region (residues 125, 126, and 151), one in the upstream connector region (residues 34 and 43), and one in the C-terminal portion of the ectodomain (residue 277). A mutant that carried amino acid substitutions at the three glycosylation sites failed to block apoptosis but behaved like wild-type gD in all other assays. The mutations that inhibited polykaryocyte formation were located in the upstream connector region (residues 34 and 43), at the alpha1 helix (residue 77), in the immunoglobulin core and downstream regions (residue 151 and 187), and at the alpha3 helix (residues 243 and 246). Binding of soluble nectin1-Fc to cells expressing the mutant gDs was generally affected by the same mutations that affected fusion, with one notable exception (Delta277-310), which affected fusion without hampering nectin1 binding. This deletion likely identifies a region of gD involved in fusion activity at a post-nectin1-binding step. We conclude that whereas mutations that affected all functions (e.g., upstream connector region and residue 151) may be detrimental to overall gD structure, the mutations that affect specific activities identify domains of gD involved in the interactions with entry receptors and fusogenic glycoproteins and with cellular proteins required to block apoptosis. The evidence that glycosylation of gD is required for blocking apoptosis supports the conclusion that the interacting protein is the mannose-6 phosphate receptor.
DNA-binding protein activated by gamma radiation in human cells. (1990)

DNA damage-inducible responses in mammalian cells tend to lack specificity and can be activated by any one of a number of damaging agents. Although a number of different induced proteins have been described, their involvement in DNA processing and transcriptional control remains unresolved. We describe the appearance of a previously unreported, specific DNA-binding protein in nuclei from human cells exposed to ionizing radiation, which was not detected in nuclear extracts from unperturbed cells. The distal part of the simian virus 40 enhancer (without the AP-1 site) and oligonucleotide sequences derived from that sequence were used in binding studies. The appearance of this activity was dose dependent and transient, reaching a maximum at 1 h postirradiation and disappearing from nuclei by 9 h. This protein was induced in cells by a mechanism not requiring de novo protein synthesis, and the response was specific for ionizing radiation and radiomimetic agents; neither UV nor heat shock invoked a response. The DNA-binding protein was present in the cytoplasm of untreated cells, apparently being translocated to the nucleus only after radiation exposure. Southwestern (DNA-protein) analysis demonstrated that the nuclear and cytoplasmic proteins were approximately the same size, 43,000 daltons. The protected DNA-binding motif, using the distal fragment of the simian virus 40 enhancer as the substrate, was shown by DNase I footprint analysis to be pTGTCAGTTAGGGTACAGTCAATCCCAp. This was confirmed by dimethyl sulfate footprinting.
Localized Immunotherapy via Liposome-Anchored Anti-CD137 + IL-2 Prevents Lethal Toxicity and Elicits Local and Systemic Antitumor Immunity (2013)

Immunostimulatory agonists such as anti-CD137 and interleukin (IL)-2 have elicited potent antitumor immune responses in preclinical studies, but their clinical use is limited by inflammatory toxicities that result upon systemic administration. We hypothesized that by rigorously restricting the biodistribution of immunotherapeutic agents to a locally accessible lesion and draining lymph node(s), effective local and systemic antitumor immunity could be achieved in the absence of systemic toxicity. We anchored anti-CD137 and an engineered IL-2Fc fusion protein to the surfaces of PEGylated liposomes, whose physical size permitted dissemination in the tumor parenchyma and tumor-draining lymph nodes but blocked entry into the systemic circulation following intratumoral injection. In the B16F10 melanoma model, intratumoral liposome-coupled anti-CD137 + IL-2Fc therapy cured a majority of established primary tumors while avoiding the lethal inflammatory toxicities caused by equivalent intratumoral doses of soluble immunotherapy. Immunoliposome therapy induced protective antitumor memory and elicited systemic antitumor immunity that significantly inhibited the growth of simultaneously established distal tumors. Tumor inhibition was CD8(+) T-cell-dependent and was associated with increased CD8(+) T-cell infiltration in both treated and distal tumors, enhanced activation of tumor antigen-specific T cells in draining lymph nodes, and a reduction in regulatory T cells in treated tumors. These data suggest that local nanoparticle-anchored delivery of immuno-agonists represents a promising strategy to improve the therapeutic window and clinical applicability of highly potent but otherwise intolerable regimens of cancer immunotherapy. Cancer Res; 73(5); 1547-58. ©2012 AACR.
A Large-Swing Transformer-Boosted Serial Link Transmitter With $&gt;{\rm V}_{\rm DD}$ Swing (2007)

The design and analysis of a large-swing transformer-boosted serial link transmitter is described. Transformer boosting is used to produce a signal swing that is not constrained by the supply voltage and enables a true pre-emphasis transmitter with a differential output swing greater than the supply. The boosted signal is separated from the driver through series inductors and therefore does not stress the transistor voltage tolerance. Several design tradeoffs between the amounts of boosting, power, and output matching are examined in both analysis and simulation. Distributed boosting is employed to relax the tradeoff between the amount of boosting and output matching degradation. Implemented in a 0.13-mum CMOS technology, the prototype chip produces an 8-Gb/s PRBS 2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">31</sup> -1 data pattern and achieves a 1.42 V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">pp</sub> differential output swing while drawing 137 mA current from a 1.2-V supply. The measured output reflection coefficient is better than -10dB up to 4 GHz
Memristor Bridge Synapse-Based Neural Network and Its Learning (2012)

Analog hardware architecture of a memristor bridge synapse-based multilayer neural network and its learning scheme is proposed. The use of memristor bridge synapse in the proposed architecture solves one of the major problems, regarding nonvolatile weight storage in analog neural network implementations. To compensate for the spatial nonuniformity and nonideal response of the memristor bridge synapse, a modified chip-in-the-loop learning scheme suitable for the proposed neural network architecture is also proposed. In the proposed method, the initial learning is conducted in software, and the behavior of the software-trained network is learned by the hardware network by learning each of the single-layered neurons of the network independently. The forward calculation of the single-layered neuron learning is implemented on circuit hardware, and followed by a weight updating phase assisted by a host computer. Unlike conventional chip-in-the-loop learning, the need for the readout of synaptic weights for calculating weight updates in each epoch is eliminated by virtue of the memristor bridge synapse and the proposed learning scheme. The hardware architecture along with the successful implementation of proposed learning on a three-bit parity network, and on a car detection network is also presented.
Genes for the Biosynthesis of the Fungal Polyketides Hypothemycin from <i>Hypomyces subiculosus</i> and Radicicol from <i>Pochonia chlamydosporia</i> (2008)

Gene clusters for biosynthesis of the fungal polyketides hypothemycin and radicicol from Hypomyces subiculosus and Pochonia chlamydosporia, respectively, were sequenced. Both clusters encode a reducing polyketide synthase (PKS) and a nonreducing PKS like those in the zearalenone cluster of Gibberella zeae, plus enzymes with putative post-PKS functions. Introduction of an O-methyltransferase (OMT) knockout construct into H. subiculosus resulted in a strain with increased production of 4-O-desmethylhypothemycin, but because transformation of H. subiculosus was very difficult, we opted to characterize hypothemycin biosynthesis using heterologous gene expression. In vitro, the OMT could methylate various substrates lacking a 4-O-methyl group, and the flavin-dependent monooxygenase (FMO) could epoxidate substrates with a 1',2' double bond. The glutathione S-transferase catalyzed cis-trans isomerization of the 7',8' double bond of hypothemycin. Expression of both hypothemycin PKS genes (but neither gene alone) in yeast resulted in production of trans-7',8'-dehydrozearalenol (DHZ). Adding expression of OMT, expression of FMO, and expression of cytochrome P450 to the strain resulted in methylation, 1',2'-epoxidation, and hydroxylation of DHZ, respectively. The radicicol gene cluster encodes halogenase and cytochrome P450 homologues that are presumed to catalyze chlorination and epoxidation, respectively. Schemes for biosynthesis of hypothemycin and radicicol are proposed. The PKSs encoded by the two clusters described above and those encoded by the zearalenone cluster all synthesize different products, yet they have significant sequence identity. These PKSs may provide a useful system for probing the mechanisms of fungal PKS programming.
Analysis of a biodegradable composite for bone healing (1996)

A degradable L-PLA/calcium carbonate composite made of interconnecting phases was examined. This structure was used both to slow the degradation rate and to reduce the brittleness of the ceramic. Both in vitro and in vivo degradation studies were performed. Samples were incubated in buffered saline or placed in the dorsum of rats for 0, 1, or 4 weeks. Mechanical testing was performed on both groups, volume fraction of each component was determined for in vitro samples, and histology was performed on in vivo samples. Failure load, tensile strength, and elastic modulus significantly decreased during the 1st week for both groups. Continued decreases were seen at 4 weeks for in vitro samples but not for in vivo. Failure strain and tensile strength decreased only for in vitro specimens. PLA fraction significantly decreased during the 1st week and then stabilized. Histology showed that tissue ingrowth occurred at 4 weeks. The decrease in mechanical properties was probably a result of the decreased PLA fraction. The stabilization and even a slight increase in tensile strength and failure strain in the in vivo samples was probably due to the tissue ingrowth forming an implant-tissue composite.
CHIMERIC MONOCLONAL CD4 ANTIBODY—A NOVEL IMMUNOSUPPRESSANT FOR CLINICAL HEART TRANSPLANTATION (1994)

The murine CD4 monoclonal antibody (mAb) M-T412 effectively downregulates T-helper-inducer function, while exhibiting high affinity and specificity for an epitope formed by the V1 and V2 domain of CD4. The antibody was chimerized by combining the murine VH and VL parts to the constant region of a human IgG1 kappa immunoglobulin. This chimeric CD4 monoclonal antibody (chim CD4 mAb) cM-T412 was used for adjunct immunosuppression in addition to standard triple-drug therapy for patients after orthotopic (n = 10) and heterotopic (n = 1) heart transplantation (HTx). cM-T412 was administered intraoperatively and postoperatively on days 1-7, 9, 11, 13, 17, and 21. A control group of similar composition (10 orthotopic, 1 heterotopic HTx) was conventionally treated in an adjunct fashion with antithymocyte globulin (ATG) until cyclosporine (CsA) in serum had reached therapeutic levels. Over the total observation time (mean: 600 days), the number of acute rejection episodes per 100 patient days was 0.26 in the cM-T412 group versus 0.41 in the control group, indicating a reduction of nearly 40%. Four of the 11 patients in the CD4 group have thus far not experienced any rejection crisis compared with two out of 11 in the control group. The mean time to the first rejection episode was 43.7 days in the CD4-treated patients versus 25.3 days in the control group. In addition the interval to the second rejection episode was longer in CD4 patients than in controls. Furthermore, patients treated with chim CD4 mAb had fewer episodes of infection during the first year after HTx (0.49 vs. 0.91 per 100 pt. days) and had a better overall survival rate (91% vs. 73%) than control group pts. No anaphylactic reaction was observed. The only adverse event probably related to cM-T412 infusion was a transient decrease of blood pressure in one patient. Although this study has only a limited number of patients, addition of cM-T412 to standard triple drug therapy appears to be an effective, specific, and well tolerated adjunct to current immunosuppression that offers a new approach for an improved immunomodulatory regimen after heart transplantation.
Comparison of human respiratory syncytial virus A2 and 8/60 fusion glycoprotein gene sequences and mapping of sub‐group specific antibody epitopes (2001)

The fusion glycoprotein, F, of human respiratory syncytial virus is a principal target of neutralising antibodies and an important protective immunogen. Among sub-group A strains of the virus the F gene is highly conserved. A comparison of F gene sequences of two sub-group B strains, 8/60 and 18537, indicates that the gene also is conserved within this sub-group. However, both limited sequence variability and antigenic variation occurs between F genes from different virus sub-groups. Such variability may be important in the failure of natural- and vaccine-induced immunity and it is thus important to identify the variable epitopes. Three anti-F MAbs exhibiting sub-group specific neutralisation and binding to recombinant F glycoprotein were studied. Comparison of A2 and 8/60 F gene sequences revealed 64 predicted varient amino acids. In order to map the variant amino acids responsible for sub-group specific binding, three sets of chimaeric genes, in which different domains of A2 and 8/60 F were exchanged, were created and expressed. Sub-group specificity mapped to the N-terminal region of F1 for two MAbs (RS2B8 and RS348) and to the C-terminal region for the third. By using site-directed mutagenesis, sub-group specific binding of MAbs RS2B8 and RS348 was attributed to a predicted loop region between residues 200 and 216. This loop carried four residues variant between the sub-groups. Change of at least two was necessary to abrogate MAb binding. J. Med. Virol. 63:168–177, 2001. © 2001 Wiley-Liss, Inc.
Polysome immunoprecipitation of phenylalanine hydroxylase mRNA from rat liver and cloning of its cDNA. (1982)

The mRNA for phenylalanine hydroxylase (phenylalanine 4-monooxygenase, EC 1.14.16.1) has been purified from total rat liver mRNAs, of which it constitutes less than 0.25%, to greater than 10% purity in a single step by specific polysome immunoprecipitation. The purified mRNA was used for synthesis and cloning of its cDNA. Recombinant colonies containing phenylalanine hydroxylase DNA sequences were identified by differential hybridization, hybrid-selected translation, and blot hybridization analysis. The rat cDNA clone was capable of hybridizing with human phenylalanine hydroxylase mRNA, which will permit the isolation of the corresponding human gene for analysis of phenylketonuria, a hereditary disorder in phenylalanine metabolism that causes permanent mental retardation in humans.
Analysis and Protection of Dynamic Membership Information for Group Key Distribution Schemes (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> In secure group-oriented applications, key management schemes are employed to distribute and update keys such that unauthorized parties cannot access group communications. Key management, however, can disclose information about the dynamics of group membership, such as the group size and the number of joining and departing users. This is a threat to applications with confidential group membership information. This paper investigates techniques that can stealthily acquire group dynamic information from key management. We show that insiders and outsiders can successfully obtain group membership information by exploiting key establishment and key updating procedures in many popular key management schemes. Particularly, we develop three attack methods targeting tree-based centralized key management schemes. Further, we propose a defense technique utilizing batch rekeying and phantom users, and derive performance criteria that describe security level of the proposed scheme using mutual information. The proposed defense scheme is evaluated based on the data from MBone multicast sessions. We also provide a brief analysis on the disclosure of group dynamic information in contributory key management schemes. </para>
Coupled Wave Theory and Waveguide Applications (1954)

Some theory describing the behavior of two coupled waves is presented, and it is shown that this theory applies to coupled transmission lines. A loose-coupling theory, applicable when very little power is transferred between the coupled waves, shows how to taper the coupling distribution to minimize the length of the coupling region. A tight-coupling theory, applicable when the coupling is uniform along the direction of wave propagation, shows that a periodic exchange of energy between coupled waves takes place provided that the attenuation and phase constants (α <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> and β respectively) are both equal, or provided that the phase constants are equal and the difference between the attenuation constants (α <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> — α <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> ) is small compared to the coefficient of coupling c. Either (α <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> — α <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> )/c or (β <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> — β <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> )/c being large compared to unity is sufficient to prevent appreciable energy exchange between the coupled waves. Experimental work has confirmed the theory. Applications include highly efficient pure-mode transducers in multi-mode systems, and frequency-selective filters.
Scaling Deep Learning-Based Decoding of Polar Codes via Partitioning (2017)

The training complexity of deep learning-based channel decoders scales exponentially with the codebook size and therefore with the number of information bits. Thus, neural network decoding (NND) is currently only feasible for very short block lengths. In this work, we show that the conventional iterative decoding algorithm for polar codes can be enhanced when sub-blocks of the decoder are replaced by neural network (NN) based components. Thus, we partition the encoding graph into smaller sub-blocks and train them individually, closely approaching maximum a posteriori (MAP) performance per sub-block. These blocks are then connected via the remaining conventional belief propagation decoding stage(s). The resulting decoding algorithm is non-iterative and inherently enables a highlevel of parallelization, while showing a competitive bit error rate (BER) performance. We examine the degradation through partitioning and compare the resulting decoder to state-of-the art polar decoders such as successive cancellation list and belief propagation decoding.
The design of dual-mode photochromic and electrochromic 1,2-Dithienylcyclopentene dyes (2008)

Chemicals that interconvert between colourless and coloured states upon stimulation with light or electricity are key to development of modern optical filtering technologies. Such chemicals are found in photochromic lenses or electrochromic windows that darken when exposed to intense sunlight or by the flick of a switch, respectively. This thesis proposes the design of chemical dyes that change colour when exposed to both intense light and electricity: offering access to an advanced set of materials useful for designing dual-mode photochromic and electrochromic hybrid technologies. Photochromic 1,2-dithienylcyclopentene dyes (DTEs) reversibly interconvert between their colourless ring-open and coloured ring-closed forms upon irradiation with appropriate wavelengths of light. Recent findings have shown that DTEs are also electrochromic and change colours when they are subject to electrochemical oxidation. However, to date, the electrochromism of DTEs is not reversible. This thesis presents DTE derivatives that are capable of being toggled between multiple oxidation states and shows that reversible electrochromism of DTEs is achievable. The electrochemical reduction of a known bis(N-methylpyridinium) DTE is explored and is shown to undergo a ring-closing reaction using a combination of cyclic voltammetry and various spectroelectrochemical analyses. The bis(N-methylpyridinium) motif is then used to design and evaluate the electrochromic performance of three DTE derivatives that undergo reductive ring-closing and oxidative ring-opening reactions. All three DTEs undergo ring-closing isomerization reactions when irradiated with UV light or when electrochemically reduced. Conversely, all three DTEs are ring-opened by irradiation with visible light or by electrochemical oxidation. A structural dependence for the thermal, photochemical and electrochemical properties of the DTE derivatives is thoroughly investigated and discussed. The results of a collaboration to characterize the electrochemical properties of N-heterocyclic carbene (NHC) reagents and their corresponding imidazolium conjugate acid ions are also reported as an appendix. NHCs are most noted for their role as coordinating ligands in modern organometallic catalysts, while imidazolium ions are important to the design of ionic liquids. The results of these electrochemical studies show that 1) NHCs undergo electrochemical oxidation and are reducing agents, and 2) the electrochemical reduction of imidazolium ions is a convenient method to synthesize NHC reagents.