gebhart/patrepeval huggingface dataset:
A single VH family and long CDR3s are the targets for hypermutation in bovine immunoglobulin heavy chains (1998)

Bovine immunoglobulins are made from genes belonging to a small family of closely related VH genes. In this respect cattle resemble all species of domesticated mammals, which also use one VH family. The family, named BoVH1, is homologous to the mouse Q52 family, and there are no more than 20 genes of this family in the bovine genome. Another feature of bovine heavy chains is the use of long CDR3s, which have an average of 21 codons. It seems that there are several families of long, closely related D genes rich in glycine and tyrosine responsible for this length. Sequences described as targets for mutations in other species can be found in CDR1, CDR2, and the putative D genes. The mutation mechanism starts at some point between late fetal stage and birth and seems to be antigen independent. Diversity seems to be generated by hypermutation, although other mechanisms cannot be discounted at this time. Contrary to humans and mice, which have several VH gene families comprising more than 100 genes, cattle use only a few genes and long CDR3s followed by somatic mutation to generate the necessary diversity to recognize the universe of antigens they will encounter during their life.
Synthesis, biodistribution and imaging properties of indium-111-DTPA-paclitaxel in mice bearing mammary tumors. (1997)

These studies suggest that 111In-DTPA-paclitaxel may be clinically useful in studying the uptake of paclitaxel in solid tumors.
Recent advances in the biochemistry of polyamines in eukaryotes (1986)

AdoMet Decarboxylated AdoMet " (2) 0 2 AdoMet MTA MTA 3-Acetamidopropanal Acetyl-CoA (4) N'-ACETYLSPERMINE SPERMINE Acetyl-CoA Fig. 1. Pathway for biosynthesis and interconversion of polyamines
Multiple Activities in Lantibiotics - Models for the Design of Novel Antibiotics? (2002)

Lantibiotics are antibiotic peptides distinguished by the presence of the rare thioether amino acids lanthionine and/or methyllanthionine. They are produced by Gram-positive bacteria as gene-encoded precursor peptides and undergo post-translational modification to generate the mature peptide. The structural gene for the prepeptide and the genes involved in biosynthesis, processing, export as well as regulation and producer strain self-protection are organized in clusters. Based on their structural and functional features lantibiotics are currently divided into two major groups. The flexible amphiphilic type-A lantibiotics act primarily by pore formation in the bacterial membrane, a mechanism which was recently shown, e.g. for nisin and epidermin, to involve the interaction with specific docking molecules such as the membrane precursor lipid II. The rather rigid and globular type-B lantibiotics inhibit enzyme functions through interaction with the respective substrates: mersacidin and actagardine inhibit the cell wall biosynthesis by complexing lipid II, whereas the cinnamycin-like peptides inhibit phospholipases by binding phosphoethanolamine. Lantibiotics have attracted much attention in recent years and undergone extensive characterization. New insights into the mode of action and structure-function relationships as well as the biochemistry and the genetics will be outlined in this review.
Global Mapping of DNA Methylation in Mouse Promoters Reveals Epigenetic Reprogramming of Pluripotency Genes (2008)

DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation. It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state. We have carried out a genome-wide promoter analysis of DNA methylation in mouse embryonic stem (ES) cells, embryonic germ (EG) cells, sperm, trophoblast stem (TS) cells, and primary embryonic fibroblasts (pMEFs). Global clustering analysis shows that methylation patterns of ES cells, EG cells, and sperm are surprisingly similar, suggesting that while the sperm is a highly specialized cell type, its promoter epigenome is already largely reprogrammed and resembles a pluripotent state. Comparisons between pluripotent tissues and pMEFs reveal that a number of pluripotency related genes, including Nanog, Lefty1 and Tdgf1, as well as the nucleosome remodeller Smarcd1, are hypomethylated in stem cells and hypermethylated in differentiated cells. Differences in promoter methylation are associated with significant differences in transcription levels in more than 60% of genes analysed. Our comparative approach to promoter methylation thus identifies gene candidates for the regulation of pluripotency and epigenetic reprogramming. While the sperm genome is, overall, similarly methylated to that of ES and EG cells, there are some key exceptions, including Nanog and Lefty1, that are highly methylated in sperm. Nanog promoter methylation is erased by active and passive demethylation after fertilisation before expression commences in the morula. In ES cells the normally active Nanog promoter is silenced when targeted by de novo methylation. Our study suggests that reprogramming of promoter methylation is one of the key determinants of the epigenetic regulation of pluripotency genes. Epigenetic reprogramming in the germline prior to fertilisation and the reprogramming of key pluripotency genes in the early embryo is thus crucial for transmission of pluripotency.
Neutrophils are major contributors to intraparenchymal lung IL-1 beta expression after hemorrhage and endotoxemia. (1998)

Acute lung injury and the acute respiratory distress syndrome (ARDS) are significant causes of morbidity and mortality following sepsis and hemorrhage. Increased IL-1beta production in the lung is important in the development of acute inflammatory lung injury. Although neutrophils are an important component of the inflammatory response that characterizes acute lung injury, there is little information to suggest that they are capable of initiating cytokine-mediated immune responses in the lung. To explore the role of neutrophils in the early stages of acute lung injury, we examined IL-1beta production by mouse lung neutrophils after hemorrhage and endotoxemia. There was a significant increase in IL-1beta expression among intraparenchymal pulmonary neutrophil/mononuclear cells (IPNMC) 1 h after hemorrhage or endotoxemia. IL-1beta was detected only in a neutrophil-rich fraction of the IPNMC, but not in T and B lymphocytes positively selected from the IPNMC. Cyclophosphamide (CTX)-treated neutropenic mice expressed significantly less IL-1beta in IPNMC after hemorrhage or endotoxemia compared with CTX-untreated controls. Immunohistochemical analysis of lung sections from mice after hemorrhage or endotoxemia revealed IL-1beta expression in infiltrating neutrophils. These data indicate that IL-1beta-producing neutrophils traffic to the lungs rapidly in response to hemorrhage or endotoxemia and support the concept that proinflammatory cytokine production by lung neutrophils may contribute to the development of lung injury after blood loss and sepsis.
Ion‐Spray Mass Spectrometry and High‐Performance Liquid Chromatography—Mass Spectrometry of Synthetic Peptide Libraries (1993)

Optimizing syntheses and characterizing complex mixtures of peptides (peptide libraries)—crucial to the search for new lead structures in drug development—is possible with ion‐spray mass spectrometry alone or combined with high‐performance liquid chromatography. This was shown in investigations of a small sublibrary made up of 48 octapeptides, which represents 1 % of the peptide pool exhibiting the murine major histocompatibility complex (MHC) class I H2‐K b restricted sequence motif, and studies of a mixture of 24 576 peptides that bind to murine MHC class I Qa‐2 a molecules.
Brain edema induced by in vitro ischemia: causal factors and neuroprotection (2003)

Decreased cerebral blood flow, hence decreased oxygen and glucose, leads to ischemic brain injury via complex pathophysiological events, including excitotoxicity, mitochondrial dysfunction, increased intracellular Ca2+, and reactive oxygen species (ROS) generation. Each of these could also contribute to cerebral edema, which is the primary cause of patient mortality after stroke. In vitro brain slices are widely used to study ischemia. Here we introduce a slice model to investigate ischemia-induced edema. Significant water gain was induced in coronal slices of rat brain by 5 min of oxygen and glucose deprivation (OGD) at 35 degrees C, with progressive edema formation after return to normoxic, normoglycemic medium. Edema increased with increasing injury severity, determined by OGD duration (5-30 min). Underlying factors were assessed using glutamate-receptor antagonists (AP5/CNQX), blockade of mitochondrial permeability transition [cyclosporin A (CsA) versus FK506], inhibition of Na+/Ca2+ exchange (KB-R7943), and ROS scavengers (ascorbate, Trolox, dimethylthiourea, Tempol). All agents except KB-R7943 and FK506 significantly attenuated edema when applied after OGD; KB-R7943 was effective when applied before OGD. Significantly, complete prevention of ischemia-induced edema was achieved with a cocktail of AP5/CNQX, CsA and Tempo applied after OGD, which demonstrates the involvement of multiple, additive mechanisms. The efficacy of this cocktail further shows the potential value of combination therapies for the treatment of cerebral ischemia.
END‐PLATE POTENTIALS IN EXPERIMENTAL AUTOIMMUNE MYASTHENIA GRAVIS IN RATS* (1976)

Rats inoculated once with nicotinic acetylcholine receptor and adjuvants had two episodes of weakness, the first being acute and transient, starting on day 8, and remitting in a few days, the second, chronic, progressive, and appearing after day 20. In the acute phase, the compound action potential and twitch evoked in weak forelimb muscles by maximal nerve stimulus were greatly reduced. Nerve action potentials were normal, however, and the muscle responded to direct electrical stimulation. Using intracellular microelectrodes, miniature end-plate potentials were difficult to find and often were low in amplitude. Many fibers were functionally denervated; no action potential or end-plate potential was evoked by nerve stimulus, although the muscle fiber responded to direct stimulation. In fibers with EEPs the number of acetylcholine quanta released by nerve impulse, the store of quanta readily available for release and the mobilization rate were low. The diaphragm was similarly, but less severely affected. Recovery from the acute phase occurred in a few days with restoration of the response of forelimb muscle to nerve stimulus, even though MEPP amplitude remained low. In the chronic phase, in both forelimb muscle and diaphragm, MEPP were more easily found, but in all rats MEPP amplitude was below normal whether or not there was weakness or a decrement in the EMG. The number of quanta released by nerve stimulus, the store, and the mobilization rate of quanta were normal in all animals. The titer of antibodies ot syngeneic acetylcholine receptor was elevated in all chronic phase animals. The chronic phase is like myasthenia gravis, but rats with MEPP amplitudes as low as those in patients with MG frequently were not weak, because the number of ACh quanta released per nerve impulse is greater in the rat than in man.
Handbook of III-V Heterojunction Bipolar Transistors (1998)

Basic Properties and Device Physics of III--V Materials. Two--Terminal Heterojunction Devices. D.C. Current Gain. Nonideal D.C. Characteristics. Thermal--Electrical Properties. Collapse of Current Gain. Failure Mechanisms and Reliability Issues. Small--Signal Properties. Epitaxial Layer Design. Geometrical Layout Design. Power Amplifier. Distortion and Noise. Switching Characteristics and Spice Models. Transistor Fabrication. Measured Transistor Performances. Appendices. Glossary of Symbols. Index.
Electric field-mediated gene transfer: characterization of DNA transfer and patterns of integration in lymphoid cells (1988)

Southern analysis of individual transfectants generated by electroporation demonstrated a strong preference for the integration of DNA in low copy number even when electroporation was performed in the presence of increasing DNA concentrations. Although transfer of multiple DNA copies was detected at higher DNA concentrations (16 pmoles/ml or greater), the average gene copy number even at 36 pmoles DNA per ml, was only 13. Multiple gene copies were integrated at either a few chromosomal sites, or at a single site within individual transfectants. Restriction endonuclease cleavage data were consistent with a random orientation of molecules within a concatemer, suggesting that the concatemer may have risen via end-to-end ligation of linear molecules, rather than by homologous recombination. Integration of exogenous DNA into the host chromosome occurred preferentially at the ends of the linear molecule. Although the linearization site was lost upon integration, endonuclease sites as close as 18 bp from the linearization site were retained. These data, as well as direct restriction mapping of the transferred genes, indicate that DNA transfer and integration occur without DNA rearrangement. Taken together, these results suggest that electroporation may offer some unique advantages for the transfer of eukaryotic genes.
Wormlike Micelles and Solution Properties of a C22-Tailed Amidosulfobetaine Surfactant (2010)

Wormlike micelles have been observed and explained in a wide variety of different types of surfactants except sulfobetaine ones. Here, we first report branched worms formed by a C22-tailed amidosulfobetaine surfactant-3-(N-erucamidopropyl-N,N-dimethyl ammonium) propane sulfonate (EDAS). Increasing EDAS concentration in the semidilute region increases the viscosity by several orders of magnitude and forms viscoelastic micellar solution of entangled and branched worms. The intermicellar branching is proved by rheological methods and Cryo-TEM observation. Besides, the rheological experiments indicate that EDAS worms show some advantages such as low overlapping concentration, insensitive to inorganic salt, stable over the whole pH range.
Ratiometric Activatable Cell‐Penetrating Peptides Provide Rapid In Vivo Readout of Thrombin Activation (2012)

In real time: thrombin activation in vivo can be imaged in real time with ratiometric activatable cell penetrating peptides (RACPPs). RACPPs are designed to combine 1) dual-emission ratioing, 2) far red to infrared wavelengths for in vivo mammalian imaging, and 3) cleavage-dependent spatial localization. The most advanced RACPP uses norleucine (Nle)-TPRSFL as a linker that increases sensitivity to thrombin by about 90-fold.
A biparatopic agonistic antibody that mimics fibroblast growth factor 21 ligand activity (2018)

Bispecific antibodies have become important formats for therapeutic discovery. They allow for potential synergy by simultaneously engaging two separate targets and enable new functions that are not possible to achieve by using a combination of two monospecific antibodies. Antagonistic antibodies dominate drug discovery today, but only a limited number of agonistic antibodies (<i>i.e.</i> those that activate receptor signaling) have been described. For receptors formed by two components, engaging both of these components simultaneously may be required for agonistic signaling. As such, bispecific antibodies may be particularly useful in activating multicomponent receptor complexes. Here, we describe a biparatopic (<i>i.e.</i> targeting two different epitopes on the same target) format that can activate the endocrine fibroblast growth factor (FGF) 21 receptor (FGFR) complex containing β-Klotho and FGFR1c. This format was constructed by grafting two different antigen-specific VH domains onto the VH and VL positions of an IgG, yielding a tetravalent binder with two potential geometries, a close and a distant, between the two paratopes. Our results revealed that the biparatopic molecule provides activities that are not observed with each paratope alone. Our approach could help address the challenges with heterogeneity inherent in other bispecific formats and could provide the means to adjust intramolecular distances of the antibody domains to drive optimal activity in a bispecific format. In conclusion, this format is versatile, is easy to construct and produce, and opens a new avenue for agonistic antibody discovery and development.
Single-Database Private Information Retrieval from Fully Homomorphic Encryption (2012)

Private Information Retrieval (PIR) allows a user to retrieve the ith bit of an n-bit database without revealing to the database server the value of i. In this paper, we present a PIR protocol with the communication complexity of O(γ logn) bits, where -y is the ciphertext size. Furthermore, we extend the PIR protocol to a private block retrieval (PBR) protocol, a natural and more practical extension of PIR in which the user retrieves a block of bits, instead of retrieving single bit. Our protocols are built on the state-of-the-art fully homomorphic encryption (FHE) techniques and provide privacy for the user if the underlying FHE scheme is semantically secure. The total communication complexity of our PBR is O(γ logm + γn/m) bits, where m is the number of blocks. The total computation complexity of our PBR is O(m logm) modular multiplications plus O(n=2) modular additions. In terms of total protocol execution time, our PBR protocol is more efficient than existing PBR protocols which usually require to compute O(n=2) modular multiplications when the size of a block in the database is large and a high-speed network is available.
Bax-induced cell death in tobacco is similar to the hypersensitive response (1999)

Bax, a death-promoting member of the Bcl-2 family of proteins, triggered cell death when expressed in plants from a tobacco mosaic virus vector. Analysis of Bax deletion mutants demonstrated a requirement for the BH1 and BH3 domains in promoting rapid cell death, whereas deletion of the carboxyl-terminal transmembrane domain completely abolished the lethality of Bax in plants. The phenotype of cell death induced by Bax closely resembled the hypersensitive response induced by wild-type tobacco mosaic virus in tobacco plants carrying the N gene. The cell death-promoting function of Bax in plants correlated with accumulation of the defense-related protein PR1, suggesting Bax activated an endogenous cell-death program in plants. In support of this view, both N gene- and Bax-mediated cell death was blocked by okadaic acid, an inhibitor of protein phosphatase activity. The ability of Bax to induce cell death and a defense reaction in plants suggests that some features of animal and plant cell death processes may be shared.
Directed differentiation and mass cultivation of pure erythroid progenitors from mouse embryonic stem cells (2004)

Differentiating embryonic stem (ES) cells are an increasingly important source of hematopoietic progenitors, useful for both basic research and clinical applications. Besides their characterization in colony assays, protocols exist for the cultivation of lymphoid, myeloid, and erythroid cells. With the possible exception of mast cells, however, long-term expansion of pure hematopoietic progenitors from ES cells has not been possible without immortalization caused by overexpression of exogenous genes. Here, we describe for the first time an efficient yet easy strategy to generate mass cultures of pure, immature erythroid progenitors from mouse ES cells (ES-EPs), using serum-free medium plus recombinant cytokines and hormones. ES-EPs represent long-lived, adult, definitive erythroid progenitors that resemble immature erythroid cells expanding in vivo during stress erythropoiesis. When exposed to terminal differentiation conditions, ES-EPs differentiated into mature, enucleated erythrocytes. Importantly, ES-EPs injected into mice did not exhibit tumorigenic potential but differentiated into normal erythrocytes. Both the virtually unlimited supply of cells and the defined culture conditions render our system a valuable tool for the analysis of factors influencing proliferation and maturation of erythroid progenitors. In addition, the system allows detailed characterization of processes during erythroid proliferation and differentiation using wild-type (wt) and genetically modified ES cells.
The Degrees-of-Freedom Region of the MIMO Interference Channel With Shannon Feedback (2013)

The two-user multiple-input multiple-output (MIMO) fast-fading interference channel (IC) with an arbitrary number of antennas at each of the four terminals is studied under the settings of Shannon feedback and output feedback, wherein channel matrices and outputs, or just the channel outputs, respectively, are available to the transmitters with a delay. While for most numbers of antennas at the four terminals, the degree-of-freedom (DoF) regions with Shannon feedback are equal to that with just delayed channel state information (CSIT), it is shown that for the rest of the MIMO ICs, the DoF region with Shannon feedback is strictly larger than the DoF region with just delayed CSIT. To realize these DoF gains with Shannon feedback, a new interference alignment scheme is obtained wherein transmitter cooperation made possible by output feedback (in addition to delayed CSIT) is employed to effect a more efficient form of interference alignment than is feasible with previously known schemes that use just delayed CSIT. The DoF region for output-only feedback is also obtained for all but a class of MIMO ICs that satisfy one of two inequalities involving the numbers of antennas. Moreover, the DoF region for Shannon feedback is shown to be applicable to two limited Shannon feedback settings where the transmitters have knowledge only of certain channel matrices and certain outputs with delay.
A single amino acid in the F2 subunit of respiratory syncytial virus fusion protein alters growth and fusogenicity (2013)

Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection in children, especially in infants less than 1 year of age. There are currently no licensed vaccines against RSV. rA2ΔM2-2 is a promising live-attenuated vaccine candidate that is currently being evaluated in the clinic. Attenuation of rA2ΔM2-2 is achieved by a single deletion of the M2-2 gene, which disrupts the balance between viral transcription and replication. Whilst performing a manufacturing feasibility study in a serum-free adapted Vero cell line, differences in growth kinetics and cytopathic effect (CPE) were identified between two rA2ΔM2-2 vaccine candidates. Comparative sequence analysis identified four amino acid differences between the two vaccine viruses. Recombinant rA2ΔM2-2 viruses carrying each of the four amino acid differences identified a K66E mutation in the F2 fragment of the fusion (F) protein as the cause of the growth and CPE differences. Syncytium-formation experiments with RSV F protein carrying mutations at aa 66 suggested that a change in charge at this residue within the F2 fragment can have a significant impact on fusion.