gebhart/patrepeval huggingface dataset:
Group B Streptococcus type II polysaccharide-tetanus toxoid conjugate vaccine (1992)

Group B streptococci (GBS) are the most common cause of bacterial sepsis and meningitis in neonates in the United States. Although the capsular polysaccharide of GBS is an important virulence factor, it is variably immunogenic in humans. In this report, we have increased the immunogenicity of GBS type II polysaccharide by coupling it to tetanus toxoid (TT). Like other GBS capsular polysaccharides, the type II polysaccharide has side chains terminating in sialic acid. Controlled periodate oxidation of native II polysaccharide resulted in the conversion of 7% of sialic acid residues to an analog of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. TT was conjugated to free aldehyde groups created on the oxidized sialic acid residues by reductive amination. Serum from rabbits vaccinated with type II-TT conjugate (II-TT) vaccine contained antibodies specific to type II polysaccharide as well as to TT, whereas rabbits vaccinated with uncoupled native type II polysaccharide failed to produce a type-specific antibody response. Antibodies elicited by II-TT vaccine were serotype specific and mediated phagocytosis and killing in vitro of type II GBS by human peripheral blood leukocytes. Serum from rabbits vaccinated with II-TT vaccine provided 100% protection in a mouse model of GBS type II infection. Antibodies induced by II-TT vaccine were specific for the native but not desialylated type II polysaccharide, suggesting that an important antigenic epitope of II-TT vaccine was dependent on the presence of sialic acid. Therefore, the coupling strategy which selectively modified a portion of the sialic acid residues of types II polysaccharide before coupling the polysaccharide to TT preserved the epitope essential to protective immunity and enhanced the immunogenicity of the polysaccharide.
Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis (1999)

Breakdown of basement membrane (BM) is believed to be an essential step for tumor invasion and metastases. We have previously demonstrated that matrix metalloproteinase-9 (MMP-9), the 92 kDa collagenase expression correlates with metastases in human colorectal cancer (CRC). This study explores the relationship between the 72 and 92 kDa type IV collagenase (MMP-2 and MMP-9) activities and pattern of type IV collagen expression during human colorectal tumorigenesis. Thirty-four CRC patients, including four synchronous adenomas and one synchronous liver metastases, were involved in this study. By immunohistochemical staining, type IV collagen expression was noted to be continuous in the BM of normal mucosa, adenoma and in two cases of carcinoma in situ. Limited or absent type IV collagen staining pattern was seen in 100 (19/19) and 23% (3/13) of CRC with and without metastases, respectively. By double immunostaining, MMP-9 protein expression was noted to localize within areas of limited type IV collagen staining. Similarly, type IV collagen staining was noted to be greatest in areas devoid of MMP-9 expression. Gelatin zymography detected both 92 and 72 kDa proenzyme forms in all CRC and normal mucosa extracts examined. The mean tumor/normal fold increases of the proMMP-2 and proMMP-9 enzyme forms were 1.6+/-0.1 (mean +/- SE) and 2.4+/-0.5 in adenomas, and 2.1+/-0.2 and 4.1+/-0.7 in CRC, respectively. The 62 and 82 kDa bands were present in 63 (12/19) and 74% (14/19) of CRC with metastases, compared with only 20 (3/15) and 33% (5/15) of CRC without metastases, respectively. These differences were significant (P = 0.045 and P = 0.030, respectively). Our results demonstrate that loss of BM type IV collagen along with elevations in MMP-2 and MMP-9 expression, especially the activated forms, occur during colorectal tumorigenesis. Our data suggest that control of type IV collagenase activation may be beneficial in preventing human colorectal tumor progression.
Signal-to-Noise Relationships for Coaxial Systems that Heterodyne Backscatter from the Atmosphere (1971)

This paper analyzes the signal-to-noise ratio for a coaxial laser system that heterodynes the signal backscattered from the atmospheric aerosol. The laser radiation, which is assumed to have a wavefront with a gaussian amplitude distribution, is transmitted into the atmosphere through a telescope. Radiation is collected by the same telescope and directed onto a detector where it is mixed with a local oscillator beam originating from the same laser source. The signal-to-noise ratio at the output of the detector is calculated under shot noise limited conditions. The calculation is general and applies for both near and far fields and for focused and unfocused systems. Three specific cases are considered. These are a pulsed system, a cw system illuminating an infinite target, and a cw system illuminating a target of finite extent.
Mapping of the Sites Involved in Ligand Association and Dissociation at the Extracellular Domain of the Kinase Insert Domain-containing Receptor for Vascular Endothelial Growth Factor (1998)

The kinase insert domain-containing receptor (KDR) for vascular endothelial growth factor (VEGF) has been shown to be involved in vasculogenesis and angiogenesis. This receptor is characterized by seven immunoglobulin (Ig)-like domains within its extracellular region. To identify the domains involved in VEGF binding, we constructed various deletion mutants of the extracellular region fused with the crystallizable fragment portion of an IgG and then examined the binding affinity with VEGF by means of the BIAcore biosensor assay. Deletion of the COOH-terminal two or three Ig-like domains out of a total of seven affected ligand dissociation rather than association. Further deletion of the fourth domain caused a drastic decrease in the association rate. Binding ability was abolished completely with removal of the third domain. The mutant KDR proteins lacking the NH2-terminal Ig-like domain exhibited a slightly higher association rate compared with those of the mutants having this domain. Deletion of the first two NH2-terminal Ig-like domains caused a drastic reduction in the association rate, but affinity to VEGF was retained. These results suggest that the third Ig-like domain is critical for ligand binding, the second and fourth domains are important for ligand association, and the fifth and sixth domains are required for retention of the ligand bound to the receptor molecule. The first Ig-like domain may regulate the ligand binding.
Enhanced Oligodendrogenesis and Recovery of Neurological Function by Erythropoietin After Neonatal Hypoxic/Ischemic Brain Injury (2010)

Our study demonstrates that delayed administration of EPO promotes oligodendrogenesis and attenuates white matter injury concurrently with increased neurogenesis. These effects likely contribute to the observed improvement in neurological functional outcomes.
Measuring single cell mass, volume, and density with dual suspended microchannel resonators (2013)

Cell size, measured as either volume or mass, is a fundamental indicator of cell state. Far more tightly regulated than size is density, the ratio between mass and volume, which can be used to distinguish between cell populations even when volume and mass appear to remain constant. Here we expand upon a previous method for measuring cell density involving a suspended microchannel resonator (SMR). We introduce a new device, the dual SMR, as a high-precision instrument for measuring single-cell mass, volume, and density using two resonators connected by a serpentine fluidic channel. The dual SMR designs considered herein demonstrate the critical role of channel geometry in ensuring proper mixing and damping of pressure fluctuations in microfluidic systems designed for precision measurement. We use the dual SMR to compare the physical properties of two well-known cancer cell lines: human lung cancer cell H1650 and mouse lymphoblastic leukemia cell line L1210.
A Versatile Precursor for the Synthesis of New Ruthenium Olefin Metathesis Catalysts (2001)

The ruthenium complex (IMesH2)(Cl)2(C5H5N)2RuCHPh [IMesH2 = 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene] (3) was prepared by the reaction of (IMesH2)(PCy3)(Cl)2RuCHPh (2) with an excess of pyridine. Complex 3 contains substitutionally labile pyridine and chloride ligands and serves as a versatile starting material for the synthesis of new ruthenium benzylidenes.
Interleukin-2 gene therapy in a patient with glioblastoma. (1995)

A patient with glioblastoma multiforme (GBM) who had failed conventional therapy was treated with IL-2 gene therapy. The patient received 10 subcutaneous immunizations with autologous tumor cells and fibroblasts genetically modified to secrete IL-2 by retroviral gene transfer. An antitumor immune response mediated in part by CD8+ cytotoxic T cells was demonstrated with the patient's peripheral blood mononuclear cells. A magnetic resonance imaging (MRI) scan performed 4 weeks after the highest treatment dose revealed marked tumor necrosis. These results support the evaluation of this form of IL-2 gene therapy in additional patients with glioblastoma.
Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma (1999)

This study demonstrates that biodegradable microspheres are efficient systems for drug delivery into the brain and may have future application in the treatment of brain tumors. Further studies are needed to confirm the potential of 5-FU-loaded microspheres for the radiosensitization of glioblastoma. [Please see editorial on pages 197-9, this issue].
IGSF11 gene, frequently up-regulated in intestinal-type gastric cancer, encodes adhesion molecule homologous to CXADR, FLJ22415 and ESAM (2003)

EST H04796 is reported frequently up-regulated in intestinal-type gastric cancer based on microarray analysis combined with laser-capture microdissection. Here, we identified and characterized the gene corresponding to EST H04796 by using bioinformatics. H04796 overlapped with DKFZp586B0620, and DKFZp586B0620 overlapped with IGSF11 cDNA (NM_152538). IGSF11-1 isoform without the N-terminal signal peptide corresponded to IGSF11 cDNA, while IGSF11-2 isoform with the N-terminal signal peptide to EST BI549168. IGSF11-1 isoform, consisting of exons 1a, 2a, 3a, and 4-9, was expressed in brain medulla and testis. IGSF11-2 isoform, consisting of exons 1b, and 4-9, was expressed in brain hippocampus and testis. IGSF11 gene consisting of 10 exons, was found to encode two isoforms due to alternative splicing. IGSF11 gene on human chromosome 3q13.3 was homologous to CXADR gene on 21q21.1, FLJ22415 gene on 11q24.1, and ESAM gene on 11q24.2. CXADR is a receptor for coxsackievirus and adenovirus. FLJ22415 is the human ortholog of mouse Asp5 and rat OL-16 specifically expressed in adipose tissue. ESAM is a tight junction protein selectively expressed on endothelial cells and platelets. IGSF11-2, CXADR, FLJ22415 and ESAM are type I transmembrane proteins with extracellular immunoglobulin (Ig)-like domain(s), cytoplasmic juxtamembrane domain and C-terminal PZD-binding domain. IGSF11-2 is predicted to be an adhesion molecule based on structural similarity with CXADR, FLJ22415 and ESAM. Because IGSF11 gene is frequently up-regulated in intestinal-type gastric cancer, IGSF11 protein might be clinically applied as targets for early diagnosis of gastric cancer as well as for drug delivery to gastric cancer.
Novel Role of CD8+T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4+Th1 Responses during Retrovirus Infection in Mice (2002)

CD4(+) Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8(+) T-cell responses. However, in the present study with Friend murine retrovirus (FV), the reverse was also found to be true. In the absence of a responder H-2(b) allele at major histocompatibility complex (MHC) class II loci, a single H-2D(b) MHC class I allele was sufficient for the development of a CD4(+) Th1 response to FV. This effect of H-2D(b) on CD4(+) T-cell responses was dependent on CD8(+) T cells, as demonstrated by depletion studies. A direct effect of CD8(+) T-cell help in the development of CD4(+) Th1 responses to FV was also shown in vaccine studies. Vaccination of nonresponder H-2(a/a) mice induced FV-specific responses of H-2D(d)-restricted CD8(+) cytotoxic T lymphocytes (CTL). Adoptive transfer of vaccine-primed CD8(+) T cells to naive H-2(a/a) mice prior to infection resulted in the generation of FV-specific CD4(+) Th1 responses. This novel helper effect of CD8(+) T cells could be an important mechanism in the development of CD4(+) Th1 responses following vaccinations that induce CD8(+) CTL responses. The ability of MHC class I genes to facilitate CD4(+) Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.
Modelling the reinjection of deep-water after methane extraction in Lake Kivu (2009)

The deep-water of the East African Lake Kivu contains large amounts of dissolved methane (~60 km&lt;sup&gt;3&lt;/sup&gt; STP) and carbon dioxide (~300 km&lt;sup&gt;3&lt;/sup&gt; STP). To utilize the methane as an energy resource valued at many billion dollars and to reduce the risk of an uncontrolled gas eruption, the governments of the Democratic Republic of the Congo and Rwanda have decided to begin extracting the methane. The Government of Rwanda has issued first concessions for pilot plants to start extraction in the fall 2008.&lt;br /&gt;\nThere are two major risks involved with extracting methane from Lake Kivu: (i) disrupting the lake stratification, which could increase the probability of a gas eruption, and (ii) enhancing the transport of nutrients from the deep-water to the surface water, which could negatively affect the lake ecosystem. These two risks should be kept in mind while trying to (iii) minimize the methane loss and maximize the extraction of the naturally produced methane in the lake. In this study, a one-dimensional model was developed and applied to predict the stratification, in addition to the gas and nutrient concentration profiles, for a 100 year period of various methane extraction Scenarios in Lake Kivu. The goal of the modelling is to find an optimal strategy that acceptably fulfils all three concerns (safety, lake ecology and socioeconomic benefit).&lt;br /&gt;\nThe resulting simulations let us conclude that (a) the deep-water &lt;em&gt;MUST NOT be diluted &lt;/em&gt;with surface water to adjust its density before reinjection into the lake, and that (b) the degassed deep-water can &lt;em&gt;not be reinjected above 200 m depth&lt;/em&gt;, where this would lead to both strongly increased nutrient fluxes into the surface layer and unacceptable algae growth. Despite these two restrictions it is possible to harvest ~90% of the maximal possible methane without risking a gas eruption and without sacrificing the ecological integrity of the lake. The key findings are listed in the executive summary.
Distance spectra of turbo codes using different Trellis termination methods (2000)

This paper investigates the implications of the choice of trellis termination method for Turbo codes, and illuminates the origin of the performance degradation often experienced without trellis termination. Analythical upper bounds on the performance for the ensemble of Turbo codes using different trellis termination strategies as well as performance results obtained by computer simulation are presented. For the case of uniform interleaving, the performance differences between various termination methods are relatively small, except when using no trellis termination at all.
Inhibition of FGFR2 and FGFR1 increases cisplatin sensitivity in ovarian cancer (2010)

Fibroblast Growth Factors (FGFs) have been implicated in malignant transformation, tumor mitogenesis, angiogenesis and chemoresistance. The aim of this study was to determine which FGFs and FGFRs play functional roles in epithelial ovarian cancer. Restriction enzyme analysis of mRNA revealed that transformation was associated with a switch in FGFR2 and FGFR3, from the IIIc to the IIIb isoform. There was widespread expression of FGFs, including FGF7, in all tissues but, FGF3 and FGF19 were expressed by malignant cell lines and cancer tissue but were not present in normal tissue. Using FGFR-specific shRNAi we demonstrated that reductions in FGFR2 inhibited proliferation of ovarian cancer cell lines in vitro (>50%, p < 0.006) and reduced cisplatin IC(50) (>60%, p < 0.0001). Cell cycle analysis revealed increased cisplatin sensitivity was associated with increased G(2)/M arrest and increased apoptosis. FGFR2 shRNAi reduced growth rates of ovarian tumor xenografts by 20% (p < 0.006) and when combined with cisplatin caused a 40% reduction in proliferation rates (p < 0.007). In contrast, RNAi-induced reductions in FGFR1 increased SKOV3 cell numbers, with associated changes in cell cycle but had no effect on ES2 cells. However, the cisplatin IC(50) was reduced (>50%, p < 0.0001) by FGFR1 shRNAi in both cell lines and there was increased apoptosis (46-50%) compared with control cells (35%) (p < 0.004). Together our data suggest that combining FGFR2 inhibitors with platinum-containing cytotoxic agents for the treatment of epithelial ovarian cancer may yield increased antitumor activity. However, data on the inhibition of FGFR1 suggest that broad spectrum FGFR inhibitors may have unexpected effects on proliferation.
Tetrahydrocurcumin confers protection against amyloid β-induced toxicity (2010)

Amyloid plaques and neurofibrillary tangles are the hallmarks of Alzheimer's disease. Amyloid β, a primary component of the amyloid plaques, is neurotoxic. Considerable attention has been directed toward identifying compounds with neuroprotective properties. Using rat primary hippocampal cultures, we show that tetrahydrocurcumin (THC), a metabolite of curcumin, shows a protective effect against oligomeric amyloid-β-induced toxicity. We further show that THC reduces amyloid-β-induced (i) increase in the level of reactive oxygen species, (ii) decrease in mitochondrial membrane potential, and (iii) caspase activation. In addition, we show that THC protects human neurons from oligomeric amyloid-β-induced toxicity as well. Thus, THC confers protection against amyloid-β-induced toxicity, and the antioxidant activity may contribute to its protective effect.
Identification and Biochemical Characterization of Small-Molecule Inhibitors of West Nile Virus Serine Protease by a High-Throughput Screen (2008)

West Nile virus and dengue virus are mosquito-borne flaviviruses that cause a large number of human infections each year. No vaccines or chemotherapeutics are currently available. These viruses encode a serine protease that is essential for polyprotein processing, a required step in the viral replication cycle. In this study, a high-throughput screening assay for the West Nile virus protease was employed to screen approximately 32,000 small-molecule compounds for identification of inhibitors. Lead inhibitor compounds with three distinct core chemical structures (1 to 3) were identified. In a secondary screening of selected compounds, two compounds, belonging to the 8-hydroxyquinoline family (compounds A and B) and containing core structure 1, were identified as potent inhibitors of the West Nile virus protease, with K(i) values of 3.2 +/- 0.3 microM and 3.4 +/- 0.6 microM, respectively. These compounds inhibited the dengue virus type 2 protease with K(i) values of 28.6 +/- 5.1 microM and 30.2 +/- 8.6 microM, respectively, showing some selectivity in the inhibition of these viral proteases. However, the compounds show no inhibition of cellular serine proteases, trypsin, or factor Xa. Kinetic analysis and molecular docking of compound B onto the known crystal structure of the West Nile virus protease indicate that the inhibitor binds in the substrate-binding cleft. Furthermore, compound B was capable of inhibiting West Nile virus RNA replication in cultured Vero cells (50% effective concentration, 1.4 +/- 0.4 microM; selectivity index, 100), presumably by inhibition of polyprotein processing.
Process cost and facility considerations in the selection of primary cell culture clarification technology (2013)

The bioreactor volume delineating the selection of primary clarification technology is not always easily defined. Development of a commercial scale process for the manufacture of therapeutic proteins requires scale-up from a few liters to thousands of liters. While the separation techniques used for protein purification are largely conserved across scales, the separation techniques for primary cell culture clarification vary with scale. Process models were developed to compare monoclonal antibody production costs using two cell culture clarification technologies. One process model was created for cell culture clarification by disc stack centrifugation with depth filtration. A second process model was created for clarification by multi-stage depth filtration. Analyses were performed to examine the influence of bioreactor volume, product titer, depth filter capacity, and facility utilization on overall operating costs. At bioreactor volumes <1,000 L, clarification using multi-stage depth filtration offers cost savings compared to clarification using centrifugation. For bioreactor volumes >5,000 L, clarification using centrifugation followed by depth filtration offers significant cost savings. For bioreactor volumes of ∼ 2,000 L, clarification costs are similar between depth filtration and centrifugation. At this scale, factors including facility utilization, available capital, ease of process development, implementation timelines, and process performance characterization play an important role in clarification technology selection. In the case study presented, a multi-product facility selected multi-stage depth filtration for cell culture clarification at the 500 and 2,000 L scales of operation. Facility implementation timelines, process development activities, equipment commissioning and validation, scale-up effects, and process robustness are examined.