gebhart/patrepeval huggingface dataset:
An IgG1 titre to the F1 and V antigens correlates with protection against plague in the mouse model (1999)

The objective of this study was to identify an immunological correlate of protection for a two-component subunit vaccine for plague, using a mouse model. The components of the vaccine are the F1 and V antigens of the plague-causing organism, Yersinia pestis, which are coadsorbed to alhydrogel and administered intramuscularly. The optimum molar ratio of the subunits was determined by keeping the dose-level of either subunit constant whilst varying the other and observing the effect on specific antibody titre. A two-fold molar excess of F1 to V, achieved by immunizing with 10 micrograms of each antigen, resulted in optimum antibody titres. The dose of vaccine required to protect against an upper and lower subcutaneous challenge with Y. pestis was determined by administering doses in the range 10 micrograms F1 + 10 micrograms V to 0.01 microgram F1 + 0.01 microgram V in a two-dose regimen. For animals immunized at the 1-microgram dose level or higher with F1 + V, an increase in specific IgG1 titre was observed over the 8 months post-boost and they were fully protected against a subcutaneous challenge with 10(5) colony-forming units (CFU) virulent Y. pestis at this time point. However, immunization with 5 micrograms or more of each subunit was required to achieve protection against challenge with 10(7) CFU Y. pestis. A new finding of this study is that the combined titre of the IgG1 subclass, developed to F1 plus V, correlated significantly (P < 0.05) with protection. The titres of IgG1 in vaccinated mice which correlated with 90%, 50% and 10% protection have been determined and provide a useful model to predict vaccine efficacy in man.
Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes (2007)

Epigenetic chromatin modification is a major regulator of eukaryotic gene expression, and aberrant epigenetic silencing of gene expression contributes to tumorigenesis. Histone modifications include acetylation, phosphorylation, and methylation, resulting in a combination of histone marks known collectively as the histone code. The chromatin marks at a given promoter determine, in part, whether specific promoters are in an open/active conformation or closed/repressed conformation. Dimethyl-lysine 4 histone H3 (H3K4me2) is a transcription-activating chromatin mark at gene promoters, and demethylation of this mark by the lysine-specific demethylase 1 (LSD1), a homologue of polyamine oxidases, may broadly repress gene expression. We now report that novel biguanide and bisguanidine polyamine analogues are potent inhibitors of LSD1. These analogues inhibit LSD1 in human colon carcinoma cells and affect a reexpression of multiple, aberrantly silenced genes important in the development of colon cancer, including members of the secreted frizzle-related proteins (SFRPs) and the GATA family of transcription factors. Furthermore, we demonstrate by chromatin immunoprecipitation analysis that the reexpression is concurrent with increased H3K4me2 and acetyl-H3K9 marks, decreased H3K9me1 and H3K9me2 repressive marks. We thus define important new agents for reversing aberrant repression of gene transcription.
Synthesis of 2′-O-[2-(N-Methylcarbamoyl)ethyl]ribonucleosides Using Oxa-Michael Reaction and Chemical and Biological Properties of Oligonucleotide Derivatives Incorporating These Modified Ribonucleosides (2011)

To develop oligonucleotides containing new 2'-O-modified ribonucleosides as nucleic acid drugs, we synthesized three types of ribonucleoside derivatives modified at the 2'-hydroxyl group with 2-(methoxycarbonyl)ethyl (MOCE), 2-(N-methylcarbamoyl)ethyl (MCE), and 2-(N,N-dimethylcarbamoyl)ethyl (DMCE) groups, as key intermediates, via the oxa-Michael reaction of the appropriately protected ribonucleoside (U, C, A, and G) derivatives. Among them, the 2'-O-MCE ribonucleosides were found to be the most stable under basic conditions. To study the effects of the 2'-O-modification on the nuclease resistance of oligonucleotides incorporating the 2'-O-modified ribonucleosides and their hybridization affinities for the complementary RNA and DNA strands, 2'-O-MCE-ribonucleoside phosphoramidite derivatives were successfully synthesized and subjected to the synthesis of 2'-O-MCE-oligonucleotides and 2'-O-methyl-oligonucleotides incorporating 2'-O-MCE-ribonucleosides. The 2'-O-MCE-oligonucleotides and chimeric oligomers with 2'-O-MCE and 2'-O-methyl groups thus obtained demonstrated complementary RNA strands and much higher nuclease resistances than the corresponding 2'-O-methylated species. Finally, we incorporated the 2'-O-MCE-ribonucleosides into antisense 2'-O-methyl-oligoribonucleotides to examine their exon-skipping activities in splicing reactions related to pre-mRNA of mouse dystrophin. The exon-skipping assay of these 2'-O-methyl-oligonucleotide incorporating 2'-O-MCE-uridines showed better efficacies than the corresponding 2'-O-methylated oligoribonucleotide phosphorothioate derivatives.
An Outbreak of Crimean-Congo Hemorrhagic Fever in the United Arab Emirates, 1994–1995 (1997)

A multi-faceted investigation was conducted in the United Arab Emirates to characterize the epidemiologic and ecologic factors underlying an outbreak of Crimean-Congo hemorrhagic fever (CCHF) noted in November 1994 among abattoir workers. A chart review was conducted among hospitalized suspected cases of viral hemorrhagic fever with onset between January 1994 and March 1995 coupled with serologic testing of available specimens for the presence of virus antigen and IgG and IgM antibodies by ELISA. Livestock handlers and animal skin processors were interviewed and tested for the presence of IgG antibody. Sera from imported and domestic ruminants were examined for antibody for CCHF virus, and ticks collected from these animals were tested with an antigen-capture ELISA. Thirty-five suspected cases of CCHF were identified (case fatality = 62%). Livestock market employees, abattoir workers, and animal skin processors accounted for 16 (57%) of 28 cases with known occupational status. Serologic evidence of past asymptomatic infection was noted in 12 (4%) of 291 livestock and abattoir workers but in none of the controls. Nineteen (7%) of 268 animals were positive for CCHF virus antibodies by ELISA including 12 ruminants from Somalia and Iran and five indigenous camels. One Hyalomma impeltatum and two H. excavatum from Somali cattle and one H. anatolicum from a Somali goat were positive for CCHF virus antigen.
Multiresolution green's function methods for interactive simulation of large-scale elastostatic objects (2003)

We present a framework for low-latency interactive simulation of linear elastostatic models, and other systems arising from linear elliptic partial differential equations, which makes it feasible to interactively simulate large-scale physical models. The deformation of the models is described using precomputed Green's functions (GFs), and runtime boundary value problems (BVPs) are solved using existing Capacitance Matrix Algorithms (CMAs). Multiresolution techniques are introduced to control the amount of information input and output from the solver thus making it practical to simulate and store very large models. A key component is the efficient compressed representation of the precomputed GFs using second-generation wavelets on surfaces. This aids in reducing the large memory requirement of storing the dense GF matrix, and the fast inverse wavelet transform allows for fast summation methods to be used at run-time for response synthesis. Resulting GF compression factors are directly related to interactive simulation speedup, and examples are provided with hundredfold improvements at modest error levels. We also introduce a multiresolution constraint satisfaction technique formulated as a hierarchical CMA, so named because of its use of hierarchical GFs describing the response due to hierarchical basis constraints. This direct solution approach is suitable for hard real-time simulation since it provides a mechanism for gracefully degrading to coarser resolution constraint approximations. The GFs' multiresolution displacement fields also allow for run-time adaptive multiresolution rendering.
Aesop: a tool for automated transistor sizing (1987)

This work addresses the problem of automating the electrical optimization of combinatorial MOS circuits. Improvements to a circuit's speed, area and power consumption are sought through modifications to the transistor sizes in the circuit; no changes in the circuit structure, number of gates or clocking are introduced. Linear algorithms are presented for computing optimal transistor sizes to minimize delay, area or power. These algorithms are implemented in an interactive tool, Aesop. Aesop is a powerful and fast “what-if” tool that allows the designer to explore the space of designs having optimal transistor sizes. When compared to manual designs, the circuits produced by Aesop are typically faster or have substantially lower area and power consumption. Compared to untuned circuits, Aesop typically increases circuit speed by a factor of 2 to 4. Alternatively, power consumption and transistor area can be reduced by 25 — 50% with no sacrifice in circuit speed. These improvements are computed interactively on a professional workstation for circuits containing thousands of transistors.
Small-Molecule Inhibition of Human Immunodeficiency Virus Type 1 Infection by Virus Capsid Destabilization (2010)

Human immunodeficiency virus type 1 (HIV-1) infection is dependent on the proper disassembly of the viral capsid, or "uncoating," in target cells. The HIV-1 capsid consists of a conical multimeric complex of the viral capsid protein (CA) arranged in a hexagonal lattice. Mutations in CA that destabilize the viral capsid result in impaired infection owing to defects in reverse transcription in target cells. We describe here the mechanism of action of a small molecule HIV-1 inhibitor, PF-3450074 (PF74), which targets CA. PF74 acts at an early stage of HIV-1 infection and inhibits reverse transcription in target cells. We show that PF74 binds specifically to HIV-1 particles, and substitutions in CA that confer resistance to the compound prevent binding. A single point mutation in CA that stabilizes the HIV-1 core also conferred strong resistance to the virus without inhibiting compound binding. Treatment of HIV-1 particles or purified cores with PF74 destabilized the viral capsid in vitro. Furthermore, the compound induced the rapid dissolution of the HIV-1 capsid in target cells. PF74 antiviral activity was promoted by binding of the host protein cyclophilin A to the HIV-1 capsid, and PF74 and cyclosporine exhibited mutual antagonism. Our data suggest that PF74 triggers premature HIV-1 uncoating in target cells, thereby mimicking the activity of the retrovirus restriction factor TRIM5α. This study highlights uncoating as a step in the HIV-1 life cycle that is susceptible to small molecule intervention.
Tumor necrosis factor‐α production induced in T lymphocytes through the AIM/CD69 activation pathway (1992)

Human activation inducer molecule (AIM/CD69), a dimeric glycoprotein of 33 and 27 kDa, is the earliest inducible cell surface antigen expressed during lymphocyte activation, which has been also involved in lymphocyte proliferation. Although AIM is absent from peripheral blood resting lymphocytes, it is expressed by in vivo activated lymphocytes infiltrating sites of chronic inflammation in several pathologies, as well as by lymphocytes after in vitro activation with different stimuli. We have investigated the possibility that tumor necrosis factor-alpha (TNF-alpha) gene expression and protein secretion could be induced in peripheral blood T cells through the AIM/CD69 molecule. Anti-AIM monoclonal antibodies (mAb) were able to induce TNF-alpha secretion in T cells when protein kinase C (PKC) was simultaneously activated by treatment with phorbol esters. TNF-alpha secretion was detected at 24 h and peaked at day 3 upon T lymphocyte activation with anti-AIM mAb. Immunoprecipitation studies with an anti-TNF-alpha mAb from surface iodinated T cells activated through AIM, demonstrated that TNF-alpha first appeared as a cell surface molecular form of 26 kDa, which is subsequently released to the extracellular medium as the 17-kDa molecular form of TNF-alpha. AIM stimulation dramatically increased TNF-alpha mRNA levels, and this mRNA induction and subsequent TNF-alpha secretion were virtually abrogated by the immunosuppressive drug cyclosporin A. Taken together these results indicate that AIM constitutes a novel molecular pathway in T lymphocytes for induction of TNF-alpha, and suggest a relevant pathologic role for AIM+ lymphocytes located at sites of tissue injury in the pathogenesis of different chronic inflammatory diseases.
Modular Immune Organoids with Integrin Ligand Specificity Differentially Regulate Ex Vivo B Cell Activation (2016)

Germinal centers are dynamic structures within lymphoid tissues, which develop once B cells receive activating signals from surrounding immune cells. Germinal center B cells are small in number, heterogeneous, and prone to rapid apoptosis unless selected by the body to form memory B cells. Despite extensive research in the B cell differentiation process, the role of the lymphoid niche, in particular integrin ligands, in the development of early germinal center-like phenotype remains unclear. Here, we report a biomaterials-based modular immune organoid that enables development of early germinal-center phenotype in an integrin ligand-specific manner. We demonstrate the differential role of integrin α4β1- and αvβ3-binding ligands in the induction of GL7+ (GC-like) and GL7- (non-GC-like) phenotype in differentiating B cells while in the presence of CD40 ligand and interleukin-4. We further demonstrate the role of integrin ligand specificities in clustering of β3 integrin and B cell receptor on the surface of differentiated B cells in 3D organoids as compared to the classic 2D cocultures. The study demonstrates that biomaterials-based immune organoids represent an ex vivo platform technology, which recapitulates certain aspects of GC biology to understand the process of B cell differentiation and induction of immunological responses. This platform is particularly useful in understanding the role of selective biomolecular signals and the temporal dependency of immune responses to these signals.
Selection of antigenic and immunogenic mimics of hepatitis C virus using sera from patients (1996)

Using sera from hepatitis C virus (HCV)-infected patients and noninfected subjects to screen random peptide libraries displayed on phage, we selected peptides specifically reacting with sera from infected patients. These phage- borne peptides were shown to mimic distinct HCV determinants. They detected in all cases the presence of anti-HCV Abs in a large panel of patients' sera, thus demonstrating the high sensitivity of the selected peptides as diagnostic markers. In addition, this diagnostic approach allowed a detailed characterization of the individual humoral response to viral infection. Phage-displayed HCV mimics were substitutes for the authentic HCV epitopes in inducing a strong specific response against HCV when used as immunogens in mice. These results support the search for HCV mimics with the potential to elicit a protective immune response as leads for the development of a mimotope-based vaccine against viral infection.
La protéine immunodominante de <em>Cowdria ruminantium</em> Cr32 conservée dans le genre <em>Ehrlichia</em> (1993)

Serological tests for cowdriosis are hampered by cross-reacting antibodies from animals suspected to be infected with Ehrlichia species. We have monitored infections with Ehrlichia bovis, E. ovina, E. canis and E. phagocytophila in experimental animals by competitive ELISA, Western blotting and immunofluorescence using Cowdria-infected endothelial cell culture antigens. Cross-reactions due to Ehrlichia antibodies could be attributed to the recognition of epitopes on the immunodominant Cr32 Cowdria protein. This was especially true for E. canis and E. ovina, much less for E. bovis, but not at all for E. phagocytophila. In addition, strong cross-reactivity between Cowdria and antibodies to E. Chaffeenis were demonstrated. These findings are in agreement with the phylogenetic relationships, recently reported by van Vliet et al. in 1992, between Cowdria and other members of the tribe Ehrlichieae, which showed Cowdria to be closely related to E. canis and also to E. chaffeensis. Although the tests used in this study remain valuable tools under laboratory conditions, their specificity requires improvement. It is suggested to study recombinant Cowdria antigens for the development of second generation serological tests for cowdriosis.
Evidence for specific receptors for interleukin 3 on lymphokine-dependent cell lines established from long-term bone marrow cultures. (1984)

Utilizing 125I-labelled IL 3, an assay for specific IL 3 receptors on continuous cell lines was developed. The 32D-cl 23 and FDC-P1 cell lines examined were originally derived from long-term cultures of murine bone marrow supplemented with WEHI-3-conditioned media. Both of these cell lines have been shown to be absolutely dependent on IL 3, a component of WEHI-3-conditioned media, for growth in vitro. The binding of radiolabeled IL 3 to these cells was found to be specific, saturable, reversible, and time and temperature dependent. The specificity of IL 3 binding was demonstrated by the failure of a number of different lymphokines, hormones, and proteins to compete for the binding of radiolabeled IL 3. The IL 3-dependent cell lines uniquely express detectable receptors, whereas other cell lines of various types and origin known to be IL 3 independent had no detectable specific binding of IL 3. A Kd of 5.4 X 10(-11) M and a maximum binding capacity of 6.25 fmol per 1 X 10(6) cells was calculated for 32D-cl 23 from equilibrium binding studies. A similar analysis for FDC-P1 yielded a Kd of 1.7 X 10(-11) and a maximum binding capacity of 1.2 fmol per 1 X 10(6) cells. The data are consistent with the presence of 4000 to 5000 specific high-affinity binding sites/cell on 32D-cl 23, whereas FDC-P1 has 1500 to 2500 specific sites/cell. The Kd calculated for the FDC-P1 cell line from kinetic binding data was 2.5 X 10(-11) M, which agreed well with the Kd of 1.7 X 10(-11) M calculated from equilibrium data.
Full-term development after transfer of nuclei from 4-cell and compacted morula stage embryos to enucleated oocytes in the mouse (1997)

The developmental ability of enucleated mouse oocytes reconstituted between the nucleus from 4-cell mouse embryos at different cell stages and recipient cytoplasms at different conditions, and the developmental ability of oocytes receiving nuclei from compacted morulae were examined. The highest development was observed with the nucleus at the G1 stage fused with cytoplasm at the M stage. Although the enucleated oocytes receiving a nucleus from 4-cell embryos did not develop after transfer to a recipient female, young were obtained after renuclear transfer to enucleated fertilized eggs. Live mice were also obtained from the nucleus of compacted morula.
A frame mapping based HMM approach to cross-lingual voice transformation (2011)

Cross-lingual voice transformation is challenging when source language (L1) and target language (L2) are very different in corresponding phonetics and prosodies. We propose a frame mapping based HMM approach to this problem. The source speaker's speech data is first warped in frequency toward the target speaker by mapping corresponding formants of selected vowels. The parameter trajectories of the warped data are then "tiled" with the frames in target speaker's L2 data. The tiled new trajectories then form a simulated training set of target speaker in L1 and it is used to train an HMM TTS. With a bilingual (Mandarin and English) source speaker and a monolingual (English) target speaker, the frame mapping-based approach is capable of generating highly intelligible, good quality speech data in L1 (Mandarin), which sounds rather close to the target speaker. The good performance of the cross-lingual voice transformation is confirmed with speaker similarity, naturalness and intelligibility evaluations subjectively.
Nanoscale Metal−Organic Frameworks as Potential Multimodal Contrast Enhancing Agents (2006)

Nanoscale metal-organic frameworks (NMOFs) based on Gd3+ centers and benzenedicarboxylate and benzenetricarboxylate bridging ligands were synthesized using reverse microemulsions and characterized using SEM, PXRD, and TGA. These NMOFs exhibit extraordinarily large R1 and R2 relaxivities because of the presence of up to tens of millions of Gd3+ centers in each nanoparticle and are thus efficient T1 and T2 contrast agents for MRI. The NMOFs can also be made highly luminescent by doping with Eu3+ or Tb3+ centers. The results from this work suggest that NMOFs can be used as potential contrast agents for multimodal imaging.
Bacterial Spores as Vaccine Vehicles (2003)

For the first time, bacterial spores have been evaluated as vaccine vehicles. Bacillus subtilis spores displaying the tetanus toxin fragment C (TTFC) antigen were used for oral and intranasal immunization and were shown to generate mucosal and systemic responses in a murine model. TTFC-specific immunoglobulin G titers in serum (determined by enzyme-linked immunosorbent assay) reached significant levels 33 days after oral dosing, while responses against the spore coat proteins were relatively low. Tetanus antitoxin levels were sufficient to protect against an otherwise lethal challenge of tetanus toxin (20 50% lethal doses). The robustness and long-term storage properties of bacterial spores, coupled with simplified genetic manipulation and cost-effective manufacturing, make them particularly attractive vehicles for oral and intranasal vaccination.
HEADS: Headline Generation as Sequence Prediction Using an Abstract Feature-Rich Space (2015)

Carlos A. Colmenares, Marina Litvak, Amin Mantrach, Fabrizio Silvestri. Proceedings of the 2015 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies. 2015.
Cramér–Rao bounds: an evaluation tool for quantitation (2001)

The Cramér-Rao lower bounds (CRBs) are the lowest possible standard deviations of all unbiased model parameter estimates obtained from the data. Consequently they give insight into the potential performance of quantitation estimators. Using analytical CRB expressions for spectral parameters of singlets and doublets in noise, one is able to judge the precision as a function of spectral and experimental parameters. We point out the usefulness of these expressions for experimental design. The influence of constraints (chemical prior knowledge) on spectral parameters of the peaks of doublets is demonstrated and the inherent benefits for quantitation are shown. Abbreviations used: CRB Cramér-Rao lower bounds