gebhart/patrepeval huggingface dataset:
Optimization and immune recognition of multiple novel conserved HLA-A2, human immunodeficiency virus type 1-specific CTL epitopes (2003)

MHC-I-restricted cytotoxic responses are considered a critical component of protective immunity against viruses, including human immunodeficiency virus type 1 (HIV-1). CTLs directed against accessory and early regulatory HIV-1 proteins might be particularly effective; however, CTL epitopes in these proteins are rarely found. Novel artificial neural networks (ANNs) were used to quantitatively predict HLA-A2-binding CTL epitope peptides from publicly available full-length HIV-1 protein sequences. Epitopes were selected based on their novelty, predicted HLA-A2-binding affinity and conservation among HIV-1 strains. HLA-A2 binding was validated experimentally and binders were tested for their ability to induce CTL and IFN-gamma responses. About 69 % were immunogenic in HLA-A2 transgenic mice and 61 % were recognized by CD8(+) T-cells from 17 HLA-A2 HIV-1-positive patients. Thus, 31 novel conserved CTL epitopes were identified in eight HIV-1 proteins, including the first HLA-A2 minimal epitopes ever reported in the accessory and regulatory proteins Vif, Vpu and Rev. Interestingly, intermediate-binding peptides of low or no immunogenicity (i.e. subdominant epitopes) were found to be antigenic and more conserved. Such epitope peptides were anchor-optimized to improve immunogenicity and further increase the number of potential vaccine epitopes. About 67 % of anchor-optimized vaccine epitopes induced immune responses against the corresponding non-immunogenic naturally occurring epitopes. This study demonstrates the potency of ANNs for identifying putative virus CTL epitopes, and the new HIV-1 CTL epitopes identified should have significant implications for HIV-1 vaccine development. As a novel vaccine approach, it is proposed to increase the coverage of HIV variants by including multiple anchor-optimized variants of the more conserved subdominant epitopes.
The Use of Natural Polymers in Tissue Engineering: A Focus on Electrospun Extracellular Matrix Analogues (2010)

Natural polymers such as collagens, elastin, and fibrinogen make up much of the body’s native extracellular matrix (ECM). This ECM provides structure and mechanical integrity to tissues, as well as communicating with the cellular components it supports to help facilitate and regulate daily cellular processes and wound healing. An ideal tissue engineering scaffold would not only replicate the structure of this ECM, but would also replicate the many functions that the ECM performs. In the past decade, the process of electrospinning has proven effective in creating non-woven ECM analogue scaffolds of micro to nanoscale diameter fibers from an array of synthetic and natural polymers. The ability of this fabrication technique to utilize the aforementioned natural polymers to create tissue engineering scaffolds has yielded promising results, both in vitro and in vivo, due in part to the enhanced bioactivity afforded by materials normally found within the human body. This review will present the process of electrospinning and describe the use of natural polymers in the creation of bioactive ECM analogues in tissue engineering.
Extracellular vesicle-mediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells (2013)

Extracellular vesicles (EVs) carry signals within or at their limiting membranes, providing a mechanism by which cells can exchange more complex information than what was previously thought. In addition to mRNAs and microRNAs, there are DNA fragments in EVs. Solexa sequencing indicated the presence of at least 16434 genomic DNA (gDNA) fragments in the EVs from human plasma. Immunofluorescence study showed direct evidence that acridine orange-stained EV DNAs could be transferred into the cells and localize to and inside the nuclear membrane. However, whether the transferred EV DNAs are functional or not is not clear. We found that EV gDNAs could be homologously or heterologously transferred from donor cells to recipient cells, and increase gDNA-coding mRNA, protein expression, and function (e.g. AT1 receptor). An endogenous promoter of the AT1 receptor, NF-κB, could be recruited to the transferred DNAs in the nucleus, and increase the transcription of AT1 receptor in the recipient cells. Moreover, the transferred EV gDNAs have pathophysiological significance. BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia, could be transferred from K562 EVs to HEK293 cells or neutrophils. Our present study shows that the gDNAs transferred from EVs to cells have physiological significance, not only to increase the gDNA-coding mRNA and protein levels, but also to influence function in recipient cells.
Seed endosymbiosis: a vital relationship in providing prenatal care to plants (2017)

Global food security is a challenge, especially under changing climatic conditions. Recent advances in plant technology using plant-microbiome interactions promise an increased crop production. Indeed, all healthy plants or crop genotypes carry a beneficial microbiome, encompassing root- and seed-associated endosymbionts, providing mycotrophy and mycovitality to plants, respectively. Recent studies have found that mycovitality, or the endosymbiotic seed–fungus relationship and its key translational functions, bear tangible biotechnological benefits. Thus, this paper underlines the role of endophytes as early plant growth promoters under stressful environments. Notably, it explores the concept of plant prenatal care towards enhanced seed vigor, germination, and resilience, which results in an improved crop yield under stressful conditions. It presents an extensive research overview of endosymbiotic plant–fungi relationships with special focus on the wheat seed, an important source of staple food. Historical advances in terminology and scientific concepts on the subject are also presented to highlight the areas where further research is urgently needed.
Replacement of the pseudorabies virus glycoprotein gIII gene with its postulated homolog, the glycoprotein gC gene of herpes simplex virus type 1 (1989)

gIII, the major envelope glycoprotein of pseudorabies virus (PRV), shares approximately 20% amino acid similarity with glycoprotein gC of herpes simplex virus type 1 (HSV-1) and HSV-2. We describe here our first experiments on the potential conservation of function between these two genes and gene products. We constructed PRV recombinants in which the gIII gene and regulatory sequences have been replaced with the entire HSV-1 gC gene and its regulatory sequences. The gC promoter functions in the PRV genome, and authentic HSV-1 gC protein is produced, albeit at a low level, in infected cells. The gC protein is present at the cell surface but cannot be detected in the PRV envelope.
Immunoassay Standardization: Is It Possible, Who Is Responsible, Who Is Capable? (2001)

Standardization in clinical chemistry aims at improving trueness, i.e., lack of bias, but it does not directly affect assay imprecision. Standardization is important because it facilitates clinical interpretation and comparison of results from various studies (1)(2). This is especially important with analytes used for screening, and this was one reason that cholesterol assays have been standardized in the US (3). Standardization of assays for prostate-specific antigen (PSA) is important for the same reason, and also because these assays are important for monitoring of disease progression in prostate cancer. Large differences in assay calibration lead to misinterpretations of the clinical course when different assays are used (4). Variation in assays for chorionic gonadotropin (CG) (5) cause similar problems when women with pregnancy-related disorders are monitored by determination of CG in serum (6). It is a testimony of the clinical importance of standardization that the preparation of standards for PSA was initiated and carried out by a urologist, Thomas Stamey from Stanford (7).

Standardization is a fairly new concept in clinical chemistry. The notion of “comprehensive measurement systems” and various levels of reference methods evolved in the 1970s (1)(2) and was formulated by Tietz in 1979 (8). Pure standards, reference methods, and standard reference materials (SRMs) are now available for many of the most important analytes determined by conventional chemical methods, but immunoassay standardization is less well developed. Immunoassay standardization was extensively discussed at two meetings organized in 1990 and 1992 by the IFCC. At these, two standardization projects were initiated: the one for cortisol was intended to serve as a model for hapten immunoassays, the other project, for standardization of assays for CG, was intended to serve as a pilot study for protein immunoassays.

The problems associated with standardization of protein and hapten assays are different. …
Coenzyme A- and Nicotinamide Adenine Dinucleotide-dependent Branched Chain α-Keto Acid Dehydrogenase (1969)

Abstract An enzyme catalyzing oxidative decarboxylation of branched short chain α-keto acids to produce the corresponding acyl coenzyme A esters has been detected in and enriched 40-fold from the cell-free extracts of Bacillus subtilis. Thus the α-keto acid of l-isoleucine, l-α-keto-β-methylvalerate, is transformed to CO2 and α-methylbutyryl coenzyme A. Coenzyme A and NAD are required for this decarboxylation. NADP, however, is inactive to the system. Thiamine pyrophosphate does not increase the enzyme activity as much as do coenzyme A and NAD. The name α-ketoisovalerate dehydrogenase is proposed for this new enzyme since α-ketoisovalerate is found to be the best substrate among the three α-keto acids, l-α-keto-β-methylvalerate, α-ketoisovalerate, and α-ketoisocaproate which are related to l-isoleucine, l-valine, and l-leucine. The optimum pH for enzyme activity lies around 7.0. The Km for coenzyme A is 0.11 mm, whereas the Km for l-α-keto-β-methylvalerate is 1.66 mm. The enzyme is stereospecific to the l isomer of α-keto-β-methylvalerate and does not use the d isomer. Coenzyme A and NAD required for the oxidative decarboxylation can be replaced with potassium ferricyanide but the activity is much less. Sulfhydryl reactants inhibit the activity of α-ketoisovalerate dehydrogenase indicating that it includes the sulfhydryl group as an essential portion for the enzyme activity. Lack of incorporation of 14CO2 into the carboxyl carbon of α-ketoisovalerate suggests that an intermediary complex of thiamine pyrophosphate with the α-keto acid substrate rather than its decarboxylated product, the corresponding aldehyde, is involved in this oxidative decarboxylation. The enzyme is clearly distinguishable from the pyruvate dehydrogenase of B. subtilis which is inactive on the branched short chain α-keto acids, and from the α-ketoglutarate dehydrogenase which is far more unstable than the enzyme and, while detectable in crude extracts, cannot be detected in any of the purified preparations.
A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): gene transfer into cells obtained from humans deficient in HPRT. (1983)

A cDNA corresponding to the human gene for hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) has been ligated into murine retroviral vectors such that it is under the transcriptional control of viral long terminal repeats. Transfection of HPRT- cells followed by superinfection with various helper viruses has led to the rescue of chimeric virus capable of transmitting the HPRT+ phenotype to HPRT- rodent or human cells. These genetically transformed cells contain authentic human HPRT at levels similar to normal HPRT+ cells.
Animal poisoning in Europe. Part 2: Companion animals (2009)

This is the second in a series of three review articles on animal poisoning in Europe and focuses on cases in pet animals and horses in five European countries (Belgium, France, Greece, Italy and Spain) reported over the last decade. In the participating countries, dogs were the most commonly poisoned species, particularly younger animals. The majority of cases in companion animals resulted from exposure to insecticides, although rodenticides (especially anticoagulants and strychnine) posed a significant risk. In all five countries, horses and cats appeared to be more susceptible to plant toxins. Intoxications with herbicides, metals, household products and drugs for veterinary and human use were reported sporadically. The review demonstrates the importance of increased awareness so as to minimise poisoning episodes and emphasises the need to establish a European system for the recording of poisoning data.
Gold nanoparticles as novel agents for cancer therapy (2012)

Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.
Self-antigen–specific CD8+ T cell precursor frequency determines the quality of the antitumor immune response (2009)

A primary goal of cancer immunotherapy is to improve the naturally occurring, but weak, immune response to tumors. Ineffective responses to cancer vaccines may be caused, in part, by low numbers of self-reactive lymphocytes surviving negative selection. Here, we estimated the frequency of CD8(+) T cells recognizing a self-antigen to be <0.0001% ( approximately 1 in 1 million CD8(+) T cells), which is so low as to preclude a strong immune response in some mice. Supplementing this repertoire with naive antigen-specific cells increased vaccine-elicited tumor immunity and autoimmunity, but a threshold was reached whereby the transfer of increased numbers of antigen-specific cells impaired functional benefit, most likely because of intraclonal competition in the irradiated host. We show that cells primed at precursor frequencies below this competitive threshold proliferate more, acquire polyfunctionality, and eradicate tumors more effectively. This work demonstrates the functional relevance of CD8(+) T cell precursor frequency to tumor immunity and autoimmunity. Transferring optimized numbers of naive tumor-specific T cells, followed by in vivo activation, is a new approach that can be applied to human cancer immunotherapy. Further, precursor frequency as an isolated variable can be exploited to augment efficacy of clinical vaccine strategies designed to activate any antigen-specific CD8(+) T cells.
Review of Chemical Vapor Deposition of Graphene and Related Applications (2013)

Since its debut in 2004, graphene has attracted enormous interest because of its unique properties. Chemical vapor deposition (CVD) has emerged as an important method for the preparation and production of graphene for various applications since the method was first reported in 2008/2009. In this Account, we review graphene CVD on various metal substrates with an emphasis on Ni and Cu. In addition, we discuss important and representative applications of graphene formed by CVD, including as flexible transparent conductors for organic photovoltaic cells and in field effect transistors. Growth on polycrystalline Ni films leads to both monolayer and few-layer graphene with multiple layers because of the grain boundaries on Ni films. We can greatly increase the percentage of monolayer graphene by using single-crystalline Ni(111) substrates, which have smooth surface and no grain boundaries. Due to the extremely low solubility of carbon in Cu, Cu has emerged as an even better catalyst for the growth of monolayer graphene with a high percentage of single layers. The growth of graphene on Cu is a surface reaction. As a result, only one layer of graphene can form on a Cu surface, in contrast with Ni, where more than one layer can form through carbon segregation and precipitation. We also describe a method for transferring graphene sheets from the metal using polymethyl methacrylate (PMMA). CVD graphene has electronic properties that are potentially valuable in a number of applications. For example, few-layer graphene grown on Ni can function as flexible transparent conductive electrodes for organic photovoltaic cells. In addition, because we can synthesize large-grain graphene on Cu foil, such large-grain graphene has electronic properties suitable for use in field effect transistors.
Design and synthesis of a two compartment micellar system based on the self-association behavior of poly(N-acylethyleneimine) end-capped with a fluorocarbon and a hydrocarbon chain (2000)

The synthesis, characterization, and association behavior of a new class of amphiphilic polymer surfactants are described. Living cationic polymerization of 2-methyl-2-oxazoline was utilized to create a series of water-soluble polymer surfactants FPxLn, where F denotes a well defined flourinated end group C8F17CH2CH2, Px denotes the degree of polymerization and Ln a hydrocarbon end group of variable length CnH2n+1, n = 6, 8, ..., 18. The molecular weights and polydispersities of the polymers were determined by gel permeation chromatography (GPC) in chloroform. 1H NMR spectroscopy was used to calculate the number average degree of polymerization and the degree of end group modification with the hydrocarbon chain containing termination agent. The molecular weights and degree of polymerization corresponded closely to the values expected from the monomer/initiator ratio. The polydispersities were low, ranging from 1.15 to 1.20. The extent of end group modification was calculated to be a minimum of 85% for all polymers. Fluorescence experiments employing pyrene as a probe showed that these polymers form aggregates in water through self-association in the concentration range from 0.018 to 0.061 wt.-%. In addition, the micropolarity experienced by the peak ratio I1/I3 in the vibronic fluorescence spectrum of pyrene above the cmc up to 1.0 wt.-% changed from hydrocarbon-like for FPL12, FPL14, FPL16 and FPL18 to fluorocarbon-like for FPL6 and FPL8, and intermediate behavior for FPL10. Dynamic light scattering of FP25L16 showed single micelles at a concentration of 0.50 wt.-% and 2.0 wt.-% with a hydrodynamic radius of Rh = 5.5 and 6.7 nm, respectively. 19F NMR experiments were applied for FP25L16 to study the aggregation behavior of the fluorocarbon end group. T2 relaxation experiments indicated that the degree of aggregation increased linearly with polymer concentration. Moreover, the results of the T2 relaxation experiments suggested the presence of pure fluorocarbon phases consistent with those found by fluorescence spectroscopy for FP25L16.
New Trick for Splitting Water With Sunlight (2009)

At the American Chemical Society fall meeting, a team reported incorporating a mimic of the natural catalyst of photosynthesis into a solar cell to create what amounts to artificial photosynthesis: a device that turns sunlight into fuel.
The Genetic Basis of Human Vh4 Gene Family‐Associated Cross‐Reactive Idiotype Expression in CD5+ and CD5‐ Cord Blood B‐Lymphocyte Clones (1993)

In a recent study we have observed a high frequency expression of cross-reactive idiotypes encoded by genes from the relatively small VH4 family of immunoglobulin heavy chain genes in cord blood B-lymphocyte lines. Furthermore, we have demonstrated a selective pattern of expression of two VH4-associated cross-reactive idiotype (CRI) in B-lymphocyte lines established from CD5+ and CD5- cord blood B-lymphocytes. There was a restricted expression of one CRI marker recognized by the 9G4 monoclonal antibody in lines established from CD5+ B-lymphocytes but not in those established from the CD5- population. In the current study we examine the molecular basis for the selective pattern of CRI expression. Nucleotide-sequence analysis of functional immunoglobulin heavy chain (IgH) gene rearrangements in three CD5+ lines expressing the CRI recognised by 9G4 reveal that all use a single gene from the VH4 family, the V4.21 gene. However, all three lines have distinct third complementarity determining regions (CDR3) implying different clonal origins. In contrast, four cord blood cell lines (two established from CD5+ B-lymphocytes) expressing the CRI recognized by MoAb Lc1 have functional IgH gene rearrangements involving two different genes from the VH4 family, the V71-4, and V2-1 genes. Antigen specificity analysis reveals that all three 9G4-reactive lines produce antibodies that react with the I and/or i red blood cell carbohydrate antigens. These data suggest that the distinction in VH4 gene use in CD5+ B-lymphocytes in cord blood results from a selection process in vivo that shapes the repertoire of CD5+ B-lymphocytes. This study extends recent observations that the monoclonal anti-CRI antibodies 9G4 and Lc1 are markers of two distinct subgroups of proteins encoded by two subsets of genes within the VH4 family. Furthermore, it appears that amino acid residues in framework region one and complementarity determining region two are critical for the expression of the cross reactive idiotypes and the serological distinction between the two subgroups of proteins.
Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells (1983)

Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA-mismatched marrow cells.