gebhart/patrepeval huggingface dataset:
Leukotoxin As a Virulent Factor of Pasteurella Haemolytica (1992)

Pasteurella haemolytica biotype A, serotype 1 (Al) has been established as the primary agent responsible for the clinical disease and pathophysiologic events leading to acute lobar fibrinonecrotizing pneumonia associated with bovine pneumonic pasteurellosis(1,2,3).&#x0D; The bacteria produces several potential virulent factors, of which the leukotoxin (LKT) has received the most attention(4). The LKT is a heat-labile proteinaceous exotoxin, that is oxygen-stable, non-dialyzable, water soluble, and is produced in high concentrations by P.haemolytica during the logarithmic phase of growth(5). The genes that code for the synthesis and secretion of this LKT have been cloned(6). All 15 serotypes of P. haemolytica produce LKT(7). It has a molecular weight of 101-105kDa when determined by sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis(8). Attempts to purify the LKT has been futile because it is tightly bound to the LPS and there is no efficient way to remove the LPS without inactivating the LKT. It is one of a family of RTX(repeat toxins)-pore forming cytolysin which has a unique specificity, in that it is only cytocidal to ruminant leukocytes(9). This cytotoxicity is caused by the formation of pores in the cell membrane which allows the influx of calcium and results in a sequence of cell-damaging events(lO). Since this organism produces disease only in ruminants, this would support the role of LKT as a virulence factor. Indeed, several observations point to the central role that LKT has in the pathogenesis of pneumonic pasteurellosis. For example, in experimental pasteurellosis, the clinical and pathophysiologic events are dose-dependently reproduced by the intatracheal administration of live logarithmic phase P. haemolytica and not by stationary phase organisms(ll). This enhanced pathogenicity may be related to the amount of LKT produced by these different populations. Indeed, we (5) and others(12)* have shown that the logarithmic phase cells produce far greater amounts of this LKT than stationary cells. In other studies, cattle with high LKT neutralizing antibody titers have higher survival rates in the natural disease and experimental pasteurellosis than animals with low antibody titers(13).&#x0D; Although advances have been made in describing the cytolytic properties of the P.haemolytica LKT, the mechanisms by which it brings about lung injury in cattle are poorly understood. Our laboratory has long been interested in elucidating the contributions and mechanisms by which the LKT induce this acute lung injury in pneumonic pasteurellosis. Three experiments were designed to study if the LKT contributed in the genesis of lung injury in pneumonic pasteurellosis.
Structural and electrical characterization of TiO2 grown from titanium tetrakis-isopropoxide (TTIP) and TTIP/H2O ambients (1996)

Thin films of TiO2 have been deposited on silicon wafers from titanium tetrakis-isopropoxide (TTIP) and TTIP/H2O using low pressure metalorganic chemical vapor deposition. The films have been characterized by Rutherford backscattering spectrometry, forward recoil spectrometry, x-ray diffraction, and electrical techniques. Dielectric constants of approximately 30 were measured by high frequency C–V. Metal–oxide–semiconductor capacitors were fabricated using sputtered platinum as the upper electrode material. Films deposited in the presence of water vapor had a much lower quality interface with the silicon substrate. Normal thermionic emission was observed when the gate electrode was positively biased and barrier heights were extracted. Dramatically reduced leakage currents and increased barrier heights were seen after 750 °C anneals in dry oxygen. Using a ramped voltage test, capacitors were found to break down at applied fields of 3.0 MV/cm.
Allosteric Coupling in the Bacterial Adhesive Protein FimH (2013)

The protein FimH is expressed by the majority of commensal and uropathogenic strains of Escherichia coli on the tips of type 1 fimbriae and mediates adhesion via a catch bond to its ligand mannose. Crystal structures of FimH show an allosteric conformational change, but it remains unclear whether all of the observed structural differences are part of the allosteric mechanism. Here we use the protein structural analysis tool RosettaDesign combined with human insight to identify and synthesize 10 mutations in four regions that we predicted would stabilize one of the conformations of that region. The function of each variant was characterized by measuring binding to the ligand mannose, whereas the allosteric state was determined using a conformation-specific monoclonal antibody. These studies demonstrated that each region investigated was indeed part of the FimH allosteric mechanism. However, the studies strongly suggested that some regions were more tightly coupled to mannose binding and others to antibody binding. In addition, we identified many FimH variants that appear locked in the low affinity state. Knowledge of regulatory sites outside the active and effector sites as well as the ability to make FimH variants locked in the low affinity state may be crucial to the future development of novel antiadhesive and antimicrobial therapies using allosteric regulation to inhibit FimH.
The Synthesis of a γ-Keto-α-amino Acid, a Key Intermediate in the Synthesis of Monatin, a New Natural Sweetener (1993)

Abstract An efficient method was developed for the synthesis of the ketoamino acid 2, a key intermediate in the synthesis of the novel sweet compound, monatin 1. Preparation of 2 entails coupling of a suitably protected indole acetate anion to an aspartic acid derivative.
Interleukin-2 enhances the natural killer cell response to Herceptin-coated Her2 /neu-positive breast cancer cells (2001)

The Her2/neu (c-erbB-2) oncogene encodes a 185-kDa protein tyrosine kinase which is overexpressed in 20% of breast adenocarcinomas and is recognized by a humanized anti-Her2/neu monoclonal antibody (mAb) (rhu4D5 or Herceptin). Natural killer (NK) cells are capable of mediating antibody-dependent cell cytotoxicity (ADCC) against antibody-coated targets via their expression of a low-affinity receptor for IgG (FcgammaRIII or CD16). NK cells can be expanded in cancer patients via the administration of low-dose interleukin-2 (IL-2) and become potent cytotoxic effectors following exposure to high doses of IL-2. We tested IL-2-activated NK cells against Her2/neu+ (MCF-7Her2/neu) and Her2/neu- (MDA-468) breast cancer cell lines in a 4-h 51Cr-release cytotoxicity assay in the presence or absence of rhu4D5 mAb (effector : target ratio = 10 : 1). Specific lysis of rhu4D5-coated MCF-7Her2/neu and MDA-468 target cells by IL-2-activated NK cells was 35% and 3%, respectively (p < 0.05). Lysis was less than 5% when targets were treated with either the non-humanized mu4D5 mAb or control huIgG. Lysis of rhu4D5-coated MCF-7Her2/neu cells was inhibited by 80 % when NK cells were pre-treated with an anti-Fc receptor antibody prior to use in the cytotoxicity assay. Enhanced ADCC of MCF-7Her2/neu target cells was seen when the effector cells consisted of mononuclear cells obtained from a patient demonstrating significant expansion of NK cells secondary to therapy with low-dose IL-2. Serum from patients receiving infusions of rhu4D5 mAb could substitute for exogenous antibody in the ADCC assay. NK cells activated by rhu4D5-coated tumor cells in the presence of IL-2 also produced large amounts of IFN-gamma with concomitant up-regulation of cell-surface activation markers CD25 and CD69. These results lend support to the concurrent use of rhu4D5 mAb and IL-2 therapy in patients with cancers that express the Her2/neu oncogene.
State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications. (2014)

In Part I of this Review (Wang and Gao, 2014), we introduced recent advances in gene delivery technologies and explained how they have powered some of the current human gene therapy applications. In Part II, we expand the discussion on gene therapy applications, focusing on some of the most exciting clinical uses. To help readers to grasp the essence and to better organize the diverse applications, we categorize them under four gene therapy strategies: (1) gene replacement therapy for monogenic diseases, (2) gene addition for complex disorders and infectious diseases, (3) gene expression alteration targeting RNA, and (4) gene editing to introduce targeted changes in host genome. Human gene therapy started with the simple idea that replacing a faulty gene with a functional copy can cure a disease. It has been a long and bumpy road to finally translate this seemingly straightforward concept into reality. As many disease mechanisms unraveled, gene therapists have employed a gene addition strategy backed by a deep knowledge of what goes wrong in diseases and how to harness host cellular machinery to battle against diseases. Breakthroughs in other biotechnologies, such as RNA interference and genome editing by chimeric nucleases, have the potential to be integrated into gene therapy. Although clinical trials utilizing these new technologies are currently sparse, these innovations are expected to greatly broaden the scope of gene therapy in the near future.
Genomics of Renal Cell Cancer: The Biology Behind and the Therapy Ahead (2007)

Renal cell cancer (RCC) is the most lethal of the urological cancers and accounts for 3% of all adult malignancies. Despite numerous recent advances in diagnostic imaging, surgical therapy, and basic molecular understanding, many patients still experience metastatic disease. For metastatic disease patients, response rates to conventional therapies rarely exceed 15% to 25% and are associated with serious adverse effects. The recent development of novel targeted therapies based on the precise biological pathways deregulated in a particular patient has paved the way for individualized, targeted patient management. Nevertheless, to achieve this goal, it is important to delineate the molecular mechanisms underlying cancer development and progression. Genomic approaches have revolutionized the field of cancer research and have led to the rapid discovery of multiple, parallel disease hypotheses, which ultimately have to be validated in large cohorts of patients and in downstream biological experiments for translation into clinical applications. The variable course of RCC and, until recently, a paucity of therapeutic options in the event of metastasis have led to the search for diagnostic and prognostic markers. We and others have used transcriptional profiling to classify different subtypes of RCC and to identify subtype- and metastasis-specific gene signatures predictive for outcome. We discuss herein recent genomic approaches to RCC and the emerging biological pathways underlying RCC development and progression. We also speculate how genomics may affect drug development and the management of patients with RCC.
Recombinat hormones: Molecular biology and biochemistry of human recombinant follicle stimulating hormone (Puregon®) (1996)

Follicle stimulating hormone (FSH) is a heterodimeric glycoprotein hormone produced in the anterior pituitary gland. The hormone is essential in the regulation of reproductive processes, such as follicular development and ovulation. It is clinically used for treatment of anovulation and in assisted reproduction technologies such as in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Until recently, the only source for human FSH has been the urine from post-menopausal women. Such a natural source implies limited availability and potential product variability. Thus, we have cloned the genes encoding the alpha- and beta-subunits of human FSH and transfected these into Chinese hamster ovary (CHO) cells. A CHO-clone was isolated capable of secreting intact glycosylated FSH with identical amino acid sequences to natural FSH. This cell line was grown in perfusion culture and enabled us to isolate highly pure FSH (> 99%). The complexity of the charge distribution of human recombinant FSH was demonstrated by Isoelectric focusing. The observed microheterogeneity is caused by the large number of carbohydrate chain structures which are added to the four potential glycosylation sites in the alpha beta-dimer. Furthermore, the carbohydrates show a variation in their degree of sialylation which reflects the different pl values of the individual isohormones. Despite the complexity of post-translational modification, the isoform distribution of recombinant FSH produced in a CHO-cell line and grown in perfusion culture is surprisingly similar to that observed with pituitary FSH and urinary FSH. In conclusion, we have shown that FSH-gene transfected CHO-cells are capable of stable serum-free production of recombinant FSH. A process has been developed which assures the consistent and reproducible production of highly-purified recombinant FSH.
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two (2016)

Induction of immune responses against multiple antigens expressed from conventional vector platforms is often ineffective for reasons not well understood. Common methods of expressing multiple antigens within a single vector construct include the use of fusion proteins, endoprotease cleavage sites, or internal ribosome entry sites. These methods often lead to decreased expression of antigens-of-About this supplement
Benralizumab: A New Approach for the Treatment of Severe Eosinophilic Asthma (2019)

Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fcy receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma.
Genetic Variation in Hemp and Marijuana (Cannabis sativa L.) According to Amplified Fragment Length Polymorphisms* (2006)

Cannabis sativa L. (Cannabaceae) is one of the earliest known cultivated plants and is important in the global economy today as a licit and an illicit crop. Molecular markers distinguishing licit and illicit cultivars have forensic utility, but no direct comparison of hemp and marijuana amplified fragment length polymorphism (AFLP) has been made to date. Genetic variation was surveyed in three populations of fiber hemp and a potent cultivar of marijuana using AFLP markers. Ten primer pairs yielded 1206 bands, of which 88% were polymorphic. Eighteen bands represented fixed differences between all fiber populations and the drug cultivar. These markers have practical utility for (1) establishing conspiracy in the cultivation and distribution of marijuana, (2) identifying geographic sources of seized drugs, and (3) discriminating illegal, potent marijuana cultivars from hemp where the cultivation of industrial hemp is permitted.
Method for Fingerprinting Yeast Cell Wall Mannans (1969)

Controlled acetolysis of yeast mannans yields mixtures of oligosaccharides with (1-->2) and (1-->3) linkages between the mannose units, whereas the less stable (1-->6) linkages of the polysaccharide backbone are cleaved. The "fingerprints," obtained by gel filtration of the oligosaccharide mixtures, can be used to distinguish between the different yeast mannans. The general method may be useful for determining the taxonomy of yeasts and for making correlations between immunochemical reactivity and mannan structure.
Recruitment of inflammatory cells to the pleural space. Chemotactic cytokines, IL-8, and monocyte chemotactic peptide-1 in human pleural fluids. (1993)

Pleural effusions secondary to various diseases are associated with the presence of different inflammatory cells. The role of selective chemotactic cytokines in the recruitment of phagocytes to the pleural space is unclear. IL-8 and monocyte chemotactic peptide-1 (MCP-1) are recently described cytokines that are chemotactic for neutrophils and monocytes, respectively. We prospectively studied 63 patients, using strictly defined criteria for their selection. IL-8 concentrations were elevated in both empyema fluid (9.15 +/- 0.89 ng/ml) and parapneumonic effusions (4.7 +/- 0.697 ng/ml) when compared with pleural effusions secondary to other diseases. IL-8 levels were higher in empyema fluid than in parapneumonic effusions (p = 0.01). There was a significant correlation between IL-8 levels and the total numbers of neutrophils in empyema fluids (r = 0.80). Chemotactic activity for neutrophils was elevated in empyema fluid and the addition of IL-8 neutralizing serum decreased bioactivity by 32.22%. Malignant pleural effusions had the highest levels of MCP-1 (12.0 +/- 3.7 ng/ml) when compared with others. Cytology-positive pleural fluids (n = 10) had a higher level of MCP-1 than cytology-negative effusions (p = < 0.05). Malignant pleural fluid MCP-1 levels correlated (r = 0.70) with the absolute number of monocytes in the pleural fluid. Neutralization of monocyte chemotactic activity of malignant pleural fluid by specific neutralizing serum caused a 70.3% inhibition of bioactivity. Immunohistochemical staining of malignant pleural fluid localized antigenic MCP-1 to malignant cells. We conclude that both IL-8 and MCP-1 play major but not exclusive roles in the recruitment of neutrophils and monocytes from the vascular compartment to the pleural space.
Probabilistic Algorithms and the Interactive Museum Tour-Guide Robot Minerva (2000)

This paper describes Minerva, an interactive tour-guide robot that was successfully deployed in a Smithsonian museum. Minerva’s software is pervasively probabilistic, relying on explicit representations of uncertainty in perception and control. During 2 weeks of operation, the robot interacted with thousands of people, both in the museum and through the Web, traversing more than 44 km at speeds of up to 163 cm/sec in the unmodified museum.
Expression of adhesion molecules in lymphoproliferative disorders. (1992)

It has been shown that a 600 bp long cluster of cell lineage specific hypomethylated sites in the major breakpoint cluster region (M-bcr) on chromosome 22 exists in hematopoietic cells. To determine possible relationships between methylation patterns within the M-bcr and the stage of hematopoietic cell development, the M-bcr methylation status of 39 patients with leukemia and lymphoma and two patients with myelodysplastic syndrome with non-rearranged M-bcrs was examined by BgIII-HpaII digestion. In the myeloid malignancies, the presence of a hypermethylated 4.8 kb BgIII-BgIII M-bcr allele was directly proportional to the combined myeloblast and promyelocyte percentage of the specimen, whereas the presence of a 2.5 kb BgIII-HpaII allele was directly proportional to the combined percentage of monocytic cells and neutrophils. All five acute monoblastic leukemias showed a methylation pattern that closely resembled neutrophils. All of thirteen surface immunoglobulin positive B-cell malignancies showed a distinct methylation pattern consisting of three or more BgIII-HpaII restriction fragments of 2.5 kb or less in length. The B-cell precursor leukemias showed heterogeneous M-bcr methylation patterns, with four of seven showing a B-cell pattern and three showing a hypermethylated pattern with 4.8, 3.1/3.0 and/or 2.5 kb BgIII-HpaII M-bcr alleles. It is concluded that the M-bcr methylation status is related to the maturation of the neutrophil series; the surface immunoglobulin positive B-cell malignancies are characterized by a distinct, extreme hypomethylation pattern of the M-bcr; and the B-cell precursor malignancies appear to have a heterogeneous M-bcr methylation pattern.
A cytosine analog that confers enhanced potency to antisense oligonucleotides (1999)

Antisense technology is based on the ability to design potent, sequence-specific inhibitors. The G-clamp heterocycle modification, a cytosine analog that clamps on to guanine by forming an additional hydrogen bond, was rationally designed to enhance oligonucleotide/RNA hybrid affinity. A single, context-dependent substitution of a G-clamp heterocycle into a 15-mer phosphorothioate oligodeoxynucleotide (S-ON) targeting the cyclin-dependent kinase inhibitor, p27(kip1), enhanced antisense activity as compared with a previously optimized C5-propynyl-modified p27(kip1) S-ON and functionally replaced 11 C5-propynyl modifications. Dose-dependent, sequence-specific antisense inhibition was observed at nanomolar concentrations of the G-clamp S-ONs. A single nucleotide mismatch between the G-clamp S-ON and the p27(kip1) mRNA reduced the potency of the antisense ON by five-fold. A 2-base-mismatch S-ON eliminated antisense activity, confirming the sequence specificity of G-clamp-modified S-ONs. The G-clamp-substituted p27(kip1) S-ON activated RNase H-mediated cleavage and demonstrated increased in vitro binding affinity for its RNA target compared with conventional 15-mer S-ONs. Furthermore, incorporation of a single G-clamp modification into a previously optimized 20-mer phosphorothioate antisense S-ON targeting c-raf increased the potency of the S-ON 25-fold. The G-clamp heterocycle is a potent, mismatch-sensitive, automated synthesizer-compatible antisense S-ON modification that will have important applications in the elucidation of gene function, the validation of gene targets, and the development of more potent antisense-based pharmaceuticals.
Antagonistic action of caffeine against LY294002-induced apoptosis in cerebellar granule neurons. (2000)

Caffeine inhibited the activation of JNK and decreased the phosphorylation of c-Jun to protect granule neurons from LY294002-induced apoptosis.
Zeno Effect for Quantum Computation and Control (2012)

It is well known that the quantum Zeno effect can protect specific quantum states from decoherence by using projective measurements. Here we combine the theory of weak measurements with stabilizer quantum error correction and detection codes. We derive rigorous performance bounds which demonstrate that the Zeno effect can be used to protect appropriately encoded arbitrary states to arbitrary accuracy while at the same time allowing for universal quantum computation or quantum control.