gebhart/patrepeval huggingface dataset:
Genome Sequence of a Human Tumorigenic Poxvirus: Prediction of Specific Host Response-Evasion Genes (1996)

Molluscum contagiosum virus (MCV) commonly causes asymptomatic cutaneous neoplasms in children and sexually active adults as well as persistent opportunistic acquired immunodeficiency syndrome (AIDS)-associated disease. Sequencing the 190-kilobase pair genome of MCV has now revealed that the virus potentially encodes 163 proteins, of which 103 have homologs in the smallpox virus. MCV lacks counterparts to 83 genes of the smallpox virus, including those important in suppression of host responses to infection, nucleotide biosynthesis, and cell proliferation. MCV possesses 59 genes that are predicted to encode previously uncharacterized proteins, including major histocompatibility complex class I, chemokine, and glutathione peroxidase homologs, which suggests that there are MCV-specific strategies for coexistence with the human host.
How (specific) would like your T-cells today? Generating T-cell therapeutic function through TCR-gene transfer (2012)

T-cells are central players in the immune response against both pathogens and cancer. Their specificity is solely dictated by the T-cell receptor (TCR) they clonally express. As such, the genetic modification of T lymphocytes using pathogen- or cancer-specific TCRs represents an appealing strategy to generate a desired immune response from peripheral blood lymphocytes. Moreover, notable objective clinical responses were observed in terminally ill cancer patients treated with TCR-gene modified cells in several clinical trials conducted recently. Nevertheless, several key aspects of this approach are the object of intensive research aimed at improving the reliability and efficacy of this strategy. Herein, we will survey recent studies in the field of TCR-gene transfer dealing with the improvement of this approach and its application for the treatment of malignant, autoimmune, and infectious diseases.
Non-MHC-Dependent Redirected T Cells Against Tumor Cells (2010)

Adoptive transfer of T cells with restricted tumor specificity provides a promising approach to immunotherapy of cancers. However, the isolation of autologous cytotoxic T cells that recognize tumor-associated antigens is time consuming and fails in many instances. Alternatively, gene modification with tumor antigen-specific T-cell receptors (TCR) or chimeric antigen receptors (CARs) can be used to redirect the specificity of large numbers of immune cells toward the malignant cells. Chimeric antigen receptors are composed of the single-chain variable fragment (scFv) of a tumor-recognizing antibody cloned in frame with human T-cell signaling domains (e.g., CD3zeta, CD28, OX40, 4-1BB), thus combining the specificity of antibodies with the effector functions of cytotoxic T cells. Upon antigen binding, the intracellular signaling domains of the CAR initiate cellular activation mechanisms including cytokine secretion and cytolysis of the antigen-positive target cell.In this chapter, we provide detailed protocols for large-scale ex vivo expansion of T cells and manufacturing of medium-scale batches of CAR-expressing T cells for translational research by mRNA electroporation. An anti-CD19 chimeric receptor for the targeting of leukemias and lymphomas was used as a model system. We are currently scaling up the protocols to adapt them to cGMP production of a large number of redirected T cells for clinical applications.
Respiratory Tolerance in the Protection Against Asthma (2003)

Understanding the pathways involved in the induction and maintenance of respiratory tolerance to airborne allergens is important in designing new therapies for asthma and other allergic diseases that not only control disease symptoms, but also change or potentially cure the disease. Respiratory tolerance, and mucosal immunity are maintained by a complex system of defense mechanisms. Most of the inhaled environmental load is eliminated by exclusion mechanisms, which include physical barriers, such as mucus, and cilia as well as a variety of mediators with anti-microbial and immunomodulatory properties. Blanket immunosuppression is provided by alveolar macrophages, which inhibit antigen presentation and T cell responses, in addition to their role in pathogen elimination. Furthermore, there is antigen specific unresponsiveness or tolerance. This tolerance is mediated by lung dendritic cells producing IL-10, which induce the development of CD4+ T regulatory cells. The development of respiratory tolerance also depends on co-stimulation (CD86, and the ICOS-ICOSL pathway). Although exposure of the respiratory mucosa to some pathogenic agents (especially virus, and endotoxin) is associated with asthma exacerbations, microbial exposure may also promote mucosal tolerance and protection against the development of allergic diseases, but the mechanisms involved are not very well understood. Mucosal-based immunotherapy has been already used as an alternative form of allergen delivery in immunotherapy, the only available treatment that is able to reverse established allergic disease. Strategies to further improve mucosal immunotherapy include the use of modified allergen derived peptides, and adjuvants like CpG motifs.
A Formal Total Synthesis of (±) –cacalol (2007)

A formal total synthesis of Cacalol is described. Synthesis of methyl tetralin 8 has been achieved from the 5–methoxy-1-tetralone 2. The conversion of 8 into tetralol 11 has been accomplished in three steps (bromination, formylation and oxidation).
EVALUATION OF THE FLUORESCENCE POLARIZATION ASSAY AND COMPARISON TO OTHER SEROLOGICAL ASSAYS FOR DETECTION OF BRUCELLOSIS IN CERVIDS (2001)

The complement fixation test (CFT), competitive enzyme immunoassay (CELISA), indirect enzyme immunoassay (IELISA) and fluorescence polarization assay (FPA) were evaluated for the detection of antibodies to Brucella abortus and Brucella suis biotype 4 in caribou (Rangifer tarandus caribou), elk (Cervus elapus), red deer (Cervus elapus), and reindeer (Rangifer tarandus tarandus). When combining the data the FPA and the CELISA were determined to be the most suitable tests for serodiagnosis of Cervidae. The overall actual sensitivity of the CFT and the IELISA was 100%. The overall actual sensitivity for the CELISA and FPA was 99%. The overall relative specificity of the CFT (including treatment of anti-complementary data as positive or negative for analysis), the CELISA, the IELISA and the FPA were 65%, 93%, 99%, 99%, and 99%, respectively. The specificities of the buffered plate agglutination test (BPAT), the CFT, the CELISA, the FPA and the IELISA for 55 elk vaccinated with B. abortus strain 19 and tested 4 mo post vaccination were 14%, 31%, 51%, 84%, and 2%, respectively. The FPA is the diagnostic test of choice because it has sensitivity and specificity values comparable to the CELISA; it has the capability to distinguish vaccinal antibody and antibody resulting from exposure to cross-reacting organisms such as Yersinia enterocolitica 0:9 from antibody to Brucella spp. in most cases; it is technically simple to do; it is adaptable to field use and it is relatively inexpensive.
pH‐Based Regulation of Hydrogel Mechanical Properties Through Mussel‐Inspired Chemistry and Processing (2012)

The mechanical holdfast of the mussel, the byssus, is processed at acidic pH yet functions at alkaline pH. Byssi are enriched in Fe<sup>3+</sup> and catechol-containing proteins, species with chemical interactions that vary widely over the pH range of byssal processing. Currently, the link between pH, Fe<sup>3+</sup>-catechol reactions, and mechanical function are poorly understood. Herein, we describe how pH influences the mechanical performance of materials formed by reacting synthetic catechol polymers with Fe<sup>3+</sup>. Processing Fe<sup>3+</sup>-catechol polymer materials through a mussel-mimetic acidic-to-alkaline pH change leads to mechanically tough materials based on a covalent network fortified by sacrificial Fe<sup>3+</sup>-catechol coordination bonds. Our findings offer the first direct evidence of Fe<sup>3+</sup>-induced covalent cross-linking of catechol polymers, reveal additional insight into the pH dependence and mechanical role of Fe<sup>3+</sup>- catechol interactions in mussel byssi, and illustrate the wide range of physical properties accessible in synthetic materials through mimicry of mussel protein chemistry and processing.
The Molecular Mechanism of Lead Inhibition of Human Porphobilinogen Synthase (2001)

Human porphobilinogen synthase (PBGS) is a main target in lead poisoning. Human PBGS purifies with eight Zn(II) per homo-octamer; four ZnA have predominantly nonsulfur ligands, and four ZnB have predominantly sulfur ligands. Only four Zn(II) are required for activity. To better elucidate the roles of Zn(II) and Pb(II), we produced human PBGS mutants that are designed to lack either the ZnA or ZnB sites. These proteins, MinusZnA (H131A, C223A) and MinusZnB (C122A, C124A, C132A), each become purified with four Zn(II) per octamer, thus confirming an asymmetry in the human PBGS structure. MinusZnA is fully active, whereas MinusZnB is far less active, verifying an important catalytic role for ZnB and the removed cysteine residues. Kinetic properties of the mutants and wild type proteins are described. Comparison of Pb(II) inhibition of the mutants shows that ligands to both ZnA and ZnB interact with Pb(II). The ZnB ligands preferentially interact with Pb(II). At least one ZnA ligand is responsible for the slow tight binding behavior of Pb(II). The data support a novel model where a high affinity lead site is a hybrid of the ZnA and ZnB sites. We propose that the lone electron pair of Pb(II) precludes Pb(II) to function in PBGS catalysis.
<title>Survey of helmet tracking technologies</title> (1991)

Helmet-mounted sight systems track the helmet angular orientation, thereby allowing the user to readily point weapons and sensors or to cue viewing among crew members. Most helmet- mounted display applications require that the helmet orientation be measured so that the displayed information can be properly presented. Helmet-mounted sights, also referred to as head trackers or helmet trackers, have been mechanized using a variety of technologies, each having apparent advantages. The leading technology candidates include magnetic, electro- optic, and ultrasonic head tracking systems. The selection of a particular concept is usually dependent on the specific application and the associated operational requirements. A technology overview is presented describing various electro-optic, ultrasonic, and magnetic mechanizations that have been developed. The performance characteristics are summarized with an indication of the strengths and weaknesses inherent in each approach.
On universal quantization (1985)

The quantization of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> -dimensional vectors in <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R^{n}</tex> with an arbitrary probability measure, under a mean-square error constraint, is discussed. It is demonstrated that a uniform, one-dimensional quantizer followed by a noiseless digital variable-rate encoder ("entropy encoding") can yield a rate that is, for any <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> , no more than <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.754</tex> bit-per-sample higher than the rate associated with the optimal <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> -dimensionai quantizer, regardless of the probabilistic characterization of the input <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> -vector for the allowable mean-square error.
Nanoporous Hydrogen Bonded Polymeric Microparticles: Facile and Economic Production of Cross Presentation Promoting Vaccine Carriers (2014)

Nanoporous microparticles are produced in a single step based on hydrogen bonding between a neutral polymer and tannic acid. These particles are stable in physiological medium, are non‐toxic to in vitro cultured cells, and can efficiently encapsulate proteins. In vitro and in vivo experiments show that these porous hydrogen bonded microparticles are able to induce antigen‐specific cellular and humoral immune responses against encapsulated vaccine antigens. Considering the easy and low cost manufacturing of this dry powder formulation from approved readily available components, it is anticipated that this technology holds great promise for the formulation of vaccines for developing countries or for pandemic vaccines where long term storage under refrigerated conditions is a major issue. Additionally, due to the versatility of the approach facilitates straightforward co‐encapsulation of a wide variety of additional components to further modulate the immune response.
A Potential Approach for Gene Therapy Targeting Hepatoma Using a Liver-Specific Promoter on a Retroviral Vector. (1991)

Recent technological advances made in molecular biology and in vitro culture of human and other mammalian cells have led to broad medical and scientific acceptance of the feasibility of gene therapy for genetic diseases. Cancer might practically be one of the attractive targets for such therapy. For the treatment of cancer, it is important to manipulate the gene of interest such that it is expressed solely in cancer cells. We have developed a tissue-specific gene expression system, based on a tissue-specific promoter on a retroviral vector. A murine ecotropic retroviral vector was constructed in which the Escherichia coli beta-galactosidase gene served as a reporter; it was expressed under control of the albumin enhancer element and promoter. The tissue specificity of this vector was first assessed in vitro, and beta-galactosidase activity was detected exclusively in hepatoma cell lines. This recombinant retrovirus was injected directly into a subcutaneous tumor composed of transplantable murine MH-134 hepatoma cells, and expression of the gene was observed in vivo. Then this recombinant retrovirus was injected via the spleen or directly into the liver, resulting in the gene expression in dividing hepatocytes in partially hepatectomized mice, but not in nondividing hepatocytes in normal mice. Gene transfer specific to dividing hepatocytes and expression by means of retroviral vectors should possess high potential for selective elimination of hepatoma cells surrounded by nondividing normal hepatocytes.
Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. (1991)

The human proto-oncogene c-MET encodes a heterodimeric 190 kDa transmembrane protein (p190c-met) with structural features of a tyrosine kinase receptor. The ligand for this putative receptor has not yet been identified. By Northern blot hybridization we found that, among a restricted number of human tissues, c-MET is highly expressed in the liver. This prompted us to test the hypothesis of a functional interaction between the c-MET receptor and Hepatocyte Growth Factor (HGF), a heparin-binding polypeptide consisting of heavy and light chains of 65 and 35 kDa. Nanomolar concentrations of highly purified HGF added to GTL-16 cells, which overexpress the c-MET receptor, enhanced the phosphorylation on tyrosine of the p190c-met kinase. Addition of other known growth factors or serum was ineffective. The kinase activity of the c-MET receptor was also stimulated by HGF in an in vitro assay, after detergent solubilization and partial purification of p190c-met. Moreover, elution of immunoprecipitates obtained with anti-MET antibodies from GTL-16 cell lysates yielded an HGF-responsive kinase activity. These results suggest that HGF, or a growth factor structurally related to HGF, is a candidate ligand for the receptor encoded by c-MET.
Molecular characterization of quinine/quinidine drug-dependent antibody platelet interaction using monoclonal antibodies (1985)

Two murine monoclonal antibodies, FMC 25 and AN 51, directed against distinct epitopes on the glycoprotein Ib complex, have been used to further define the mechanism of quinine/quinidine drug-dependent antibody interaction with platelets. FMC 25, directed against an epitope on glycoprotein IX, had no effect on platelet aggregation induced by collagen or adenosine diphosphate and little, if any, effect on ristocetin-induced platelet agglutination. FMC 25 and its (Fab)2 fragment, however, were potent inhibitors of drug-dependent antibody-induced platelet aggregation and blocked binding of drug-dependent antibody to platelets as assessed by indirect platelet immunofluorescence. In contrast, AN 51, directed against an epitope on the alpha-subunit of glycoprotein Ib, blocked ristocetin-induced, factor VIII/von Willebrand factor (FVIII/vWF)-dependent platelet agglutination but not drug-dependent antibody-induced platelet aggregation or binding of drug-dependent antibody to platelets. Selective proteolytic removal of the majority of the alpha-subunit of glycoprotein Ib (glycocalicin) from platelets by treatment with calcium-dependent protease did not affect binding of drug-dependent antibody. In addition, a quinidine-dependent antiplatelet antibody immunoprecipitated glycoprotein Ib complex from normal platelets and the membrane-associated proteolytic remnant of the glycoprotein Ib complex from calcium-dependent protease-treated platelets. Preincubation of drug-dependent antibody with purified glycoprotein Ib complex inhibited subsequent binding of antibody to platelets, but the separated components, glycoprotein Ib and glycoprotein IX, were both ineffective, suggesting that the normal interaction between glycoprotein Ib and glycoprotein IX in the intact complex was necessary for drug-dependent antibody recognition. The functional response of platelets to drug-dependent antibody was not mediated by way of platelet Fc receptor, since aggregation of washed platelets by acetone-aggregated IgG was not inhibited by FMC 25 (Fab)2. FVIII/vWF was not required for drug-dependent antibody-induced platelet aggregation. The combined evidence is consistent with quinine/quinidine-dependent antibody-platelet interaction occurring by way of a FVIII/vWF-independent, Fc receptor-independent mechanism that probably involves binding of antibody to glycoprotein IX or the beta-subunit of glycoprotein Ib or both.
Objective Monitoring of Physical Activity Using Motion Sensors and Heart Rate (2000)

Although neither motion sensors nor heart rate are perfect markers of physical activity, they certainly eliminate subjectivity of obtaining physical activity information. The objective method of choice depends on how the measurement will be used. For example, if walking behavior is the desired outcome, then a pedometer may be sufficient. If patterns and intensity of activity over longer periods of times such as a week or longer are needed, then an accelerometer with large memory capacity should be selected. In the future, efforts should be directed towards developing an objective motion sensor as inexpensive as a pedometer but with the data acquisition capabilities of the CSA or Tritrac accelerometer. Providing simultaneous heart rate with motion is also recommended to further verify that elevated heart rate does in fact represent a physical activity response. As the cost of the electronic components continues to decrease, these activity monitor configurations may become possible.
Ophthalmic applications of infrared lasers -- thermal considerations. (1979)

An analysis of the thermal response of clear ocular media to infrared laser radiation is presented. It is shown that from a thermodynamic viewpoint, it should be feasible to use infrared lasers in both vitrectomy and thermokeratoplasty. In vitrectomy, temperature elevations from vitreous vaporization with an intraocular CO2 laser probe would be well below retinal damage threshold levels at distances greater than 2 mm from the center of the beam. In thermokeratoplasty, peak temperature elevations could be moved from the corneal epithelium back into the corneal stroma where collagen shrinkage is desired. Other potential applications for infrared lasers are presented, and the value of accurate measurement of the infrared optical properties of ocular media is emphasized.
The TIGR Human cDNA Database (2003)

The Human cDNA Database (HCD) is a repository for human cDNA sequences and related data that is curated and maintained at The Institute for Genomic Research (TIGR). The foundation of the database is ∼160,000 partial cDNA sequences that have been generated by TIGR and Human Genome Sciences (HGS). These expressed sequence tags (ESTs) were derived from 250 cDNA libraries that represent the expressed genes of 37 distinct human organs and tissues (1). A combination of these ESTs and the human ESTs from dbEST has been assembled to yield ∼56,000 consensus sequences and ∼106,000 nonoverlapping ESTs. Of these ∼162,000 distinct sequences, approx 18% display statistically significant similarity to previously known genes, whereas the remainder identify previously unknown cDNAs. The HCD data include nucleotide sequences, putative identifications of the sequences, and tissue-based expression information. New EST sequences that are acquired by TIGR are assembled and curated in an ongoing process that aims to provide a comprehensive database of human genes and their expression patterns. The development of HCD required the construction of a sister database, the Expressed Gene Anatomy Database (EGAD). This database contains a nonredundant dataset of human transcript sequences, together with information on expression patterns and cellular roles. Extensive links between HCD and EGAD permit browsing of sequence information, functional classifications, and tissue expression patterns for particular genes of interest. Owing to the random nature of large-scale EST sampling and the wide range of tissues that have been sampled, the data that can be extracted from HCD are of particular value for several common types of cDNA sequence analyses.
Muscle regeneration during hindlimb unloading results in a reduction in muscle size after reloading (2001)

The hindlimb-unloading model was used to study the ability of muscle injured in a weightless environment to recover after reloading. Satellite cell mitotic activity and DNA unit size were determined in injured and intact soleus muscles from hindlimb-unloaded and age-matched weight-bearing rats at the conclusion of 28 days of hindlimb unloading, 2 wk after reloading, and 9 wk after reloading. The body weights of hindlimb-unloaded rats were significantly (P < 0.05) less than those of weight-bearing rats at the conclusion of hindlimb unloading, but they were the same (P > 0.05) as those of weight-bearing rats 2 and 9 wk after reloading. The soleus muscle weight, soleus muscle weight-to-body weight ratio, myofiber diameter, number of nuclei per millimeter, and DNA unit size were significantly (P < 0.05) smaller for the injured soleus muscles from hindlimb-unloaded rats than for the soleus muscles from weight-bearing rats at each recovery time. Satellite cell mitotic activity was significantly (P < 0.05) higher in the injured soleus muscles from hindlimb-unloaded rats than from weight-bearing rats 2 wk after reloading, but it was the same (P > 0.05) as in the injured soleus muscles from weight-bearing rats 9 wk after reloading. The injured soleus muscles from hindlimb-unloaded rats failed to achieve weight-bearing muscle size 9 wk after reloading, because incomplete compensation for the decrease in myonuclear accretion and DNA unit size expansion occurred during the unloading period.