gebhart/patrepeval huggingface dataset:
Carcinoembryonic antigen-producing cell-specific oncolytic adenovirus, OV798, for colorectal cancer therapy. (2003)

Human carcinoembryonic antigen (CEA) is overexpressed in most colorectal cancers and has been widely used as a clinical marker for the management of colon cancer patients. The transcriptional regulatory elements (TREs) of CEA include two enhancer elements and a promoter in the 5'-flanking region of the CEA gene. By using these elements in different combinations to control reporter gene expression and the replication of adenovirus variants in various tumor cells, we have identified an optimal CEA regulatory cassette that tightly controls gene expression and viral replication in CEA-producing colon cancer cells. One of these variants, OV798, in which this regulatory cassette controls E1A expression, was further characterized. OV798 preferentially replicates in and kills CEA-producing colorectal cancer cell lines such as LoVo and SW1463, but its replication is attenuated by 1000-fold in the CEA-negative cell lines Colo-320DM (colon cancer), PA-1 (ovarian cancer), G361 (melanoma), U118 MG (glioma), and HBL-100 (human breast epithelial cell). The antitumor activity of OV798 was further examined in BALB/c nu/nu mice carrying s.c. human colon tumor xenografts. A single intratumoral administration of OV798 resulted in growth inhibition of human LoVo colon cancer xenografts. Six weeks after treatment, relative tumor volume decreased to 90% of baseline for the OV798 treatment group, compared to an increase to 1200% of baseline at 4 weeks for the vehicle-treated group. In vitro and in vivo characterization indicate that OV798 could be used as a therapy for human colon cancer.
Biosynthesis of MAM-6, an epithelial sialomucin. Evidence for involvement of a rare proteolytic cleavage step in the endoplasmic reticulum. (1988)

MAM-6 is a major epithelial sialomucin which is abundantly present at the apical surface of ductal and alveolar cells of normal tissues and on many different carcinoma cells. MAM-6, as defined by monoclonal antibodies, consists of one or two sialylated glycoproteins with apparent molecular masses of over 400 kDa under reducing as well as nonreducing conditions. The mobility and number of glycoproteins immunoprecipitated vary depending on the cell line of origin. We have employed immunoprecipitation techniques to study the biosynthesis and glycosylation of this mucin. The biosynthesis of MAM-6 was studied in the ZR-75-1 breast cancer cell line. Two glycoproteins with apparent molecular masses of approximately 450 and 650 kDa, representing the mature form, were immunoprecipitated. By pulse-chase analysis, we show that the biosynthesis of the 450-kDa glycoprotein proceeded through intermediates of 220, 200, and 500 kDa which became perceptible after 1, 4, and 30 min, respectively. The biosynthesis of the 650-kDa glycoprotein followed a similar course through 380, 350, and 700-kDa intermediates. The processing of the 220- and 350-kDa precursors involves a rare proteolytic cleavage step which occurs in the endoplasmic reticulum. The late precursors of 500/700 kDa, observed after 30 min chase, and the mature glycoproteins were generated by extensive O-linked glycosylation. The formation of the 500/700-kDa precursors was not affected by monensin. However, the final step of maturation, sialylation of the 500/700-kDa precursors, could be inhibited by monensin. The extensive O-linked glycosylation causes the apparent high molecular weight as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Our data on the biosynthesis show that the early MAM-6 precursors contain N-linked glycans, suggesting the presence of N-linked glycans on the mature MAM-6 molecule. Although the copresence of N- and O-linked glycans has been found on many molecules, no N-linked glycans have been reported on mucus glycoproteins previously.
Linezolid Pharmacia Corp. (2000)

Linezolid is an oxazolidinone developed by Pharmacia (formerly Pharmacia & Upjohn) for the treatment of multi-resistant Gram-positive infections [187765,317456]. It binds to ribosomal 50S subunits, most likely within domain V within the 23S rRNA peptidyl transferase and a secondary interaction with the 30S subunit. This results in inhibition of the initiation of protein translation at an early point, which is probably N-formylmethionyl-tRNA [335843]. No direct action on DNA or RNA synthesis has been observed [220169]. Linezolid resistance due to a 23S rRNA mutation may emerge in Enterococci during therapy with this antimicrobial, and may be associated with clinical failure [368652]. Following FDA approval, linezolid was launched in May 2000 [368526,368652]. In April 2000, the FDA approved linezolid injection, tablets and oral suspension for the treatment of patients with infections caused by Gram-positive bacteria. It is indicated for adults in the treatment of nosocomial pneumonia, community-acquired pneumonia (CAP), complicated and uncomplicated skin and skin structure infections and vancomycin-resistant enterococcus (VRE) infections caused by methicillin-resistant Staphylococcus aureus (MRSA), VRE faecium and penicillin-susceptible Streptococcus pneumoniae [363503]. The FDA, however, did not grant Pharmacia indications for linezolid in the treatment of CAP due to either penicillin-resistant S aureus (PRSA) or MRSA. In May 2000, Merrill Lynch predicted sales for 2000 to be US $50 million, rising to US $760 million in 2004 [366910]. In February 2000, P&U predicted that peak sales of the drug had the potential to reach in excess of US $750 million [358429]. In February 1999, Morgan Stanley Dean Witter predicted sales of US $40 million in 2000 rising to US $275 million in 2005 [319855]. In December 1998, Deutsche Bank predicted sales of US $100 million in 2000 rising to US $300 million in 2002 [316769].
Herpes simplex virus-1 thymidine kinase mutants created by semi-random sequence mutagenesis improve prodrug-mediated tumor cell killing. (2001)

Cancer suicide gene therapy affords the prospect of using the most optimal genes available because the source of the therapeutic gene is often irrelevant. Currently, there are numerous preclinical and clinical trials to develop tumor ablative therapies that use viral, yeast, or bacterial genes. One such gene, the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) is widely used as a suicide gene in combination with ganciclovir. In the study reported here, a restricted set of random sequences (semi-random) was introduced into the active site of HSV-1 TK, and the resulting variants were selected on the basis of their ability to confer increased ganciclovir or acyclovir sensitivity to Escherichia coli. Sequence analysis demonstrated that functional mutants contained three to five amino acid substitutions that are unique and novel combinations. On the basis of enzyme assay results, three mutants were identified for further analysis in vitro. These three mutants conferred substantial increased sensitivity to both ganciclovir and acyclovir when compared with IC50s of wild-type TK expressing rat C6 glioma cells. One mutant, SR39, was further evaluated in a xenograft tumor model in nude mice. Expression of SR39 in tumors was shown to prevent tumor growth at prodrug dosages that did not affect wild-type HSV-1 TK-expressing tumors. The use of any of these mutants as a suicide gene should provide a more effective and safer alternative to wild-type TK, because lower, less immunosuppressive doses of ganciclovir will be necessary for tumor ablation, and the use of acyclovir may now be possible.
Minicell formation by Campylobacter jejuni (1987)

Campylobacter jejuni sheds its flagella and varying proportions of the poles of the cell late in the growth cycle, resulting in the production of very small flagellated structures 0.1 to 0.3 microM in diameter. Electron microscopy revealed that these structures were minicells possessing outer membrane, cytoplasmic membrane, flagellar basal complex, and polar membrane; nucleoplasms were not seen. The initial event in the formation of these minicells involved a constriction of the cytoplasmic membrane, segregating the polar regions of the cell. The peptidoglycan layer of the cell wall was not visible, but was presumed to lyse at the separation site of minicell formation, and to reform or remain intact along the main length of the cell because the rods did not spheroplast. Finally, rupture and resealing of the outer membrane component of the wall resulted in the release of fully enclosed minicells and nonflagellated rods.
TrafficSense: Rich Monitoring of Road and Traffic Conditions us ing Mobile Smartphones (2008)

We consider the problem of monitoring road and traffic conditions in a city. Prior work in this area has required the deployment of dedicated sensors on vehicles and/or on the roadside, or the tracking of mobile phones by service providers. Furthermore, prior work has largely focused on the developed world, with its relatively simple traffic flow patterns. In fact, traffic flow in cities of the developing regions, which comprise much of the world, tends to be much more complex owing to varied road conditions (e.g., potholed roads), chaotic traffic (e.g., a lot of braking and honking), and a heterogeneous mix of vehicles (2-wheelers, 3-wheelers, cars, buses, etc.). To monitor road and traffic conditions in such a setting, we present TrafficSense, a system that performs rich sensing by piggybacking on smartphones that users carry around with them. In this paper, we focus specifically on the sensing component, which uses the accelerometer, microphone, GSM radio, and/or GPS sensors in these phones to detect potholes, bumps, braking, and honking. TrafficSense addresses several challenges including virtually reorienting the accelerometer on a phone that is at an arbitrary orientation, and performing honk detection and localization in an energy efficient manner. We also touch upon the idea of triggered sensing, where dissimilar sensors are used in tandem to conserve energy. We evaluate the effectiveness of the sensing functions in TrafficSense based on experiments conducted on the roads of Bangalore, with promising results.
Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex (2002)

Recently, several chromatin remodeling complexes in yeast, Drosophila, and mammals have been shown to contain actin and actin-related proteins (arps). However, the function of actin in these complexes is unclear. Here, we show that the mammalian SWI/SNF-like BAF complex binds to phosphatidylinositol 4,5-bisphosphate (PIP2) micelles and PIP2-containing mixed lipid vesicles, and that PIP2 binding allows the complex to associate with actin pointed ends and branch points. Actin binds to at least two distinct domains in the C terminus of the Brg1 protein, and interaction with only one of these domains is sensitive to PIP2. Based on these findings, we propose a model for PIP2 activation of actin binding by relief of intramolecular capping of actin by Brg1.
Reduction of Chocolate’s Cariogenicity by Supplementation with Sodium Caseinate (1987)

The cariogenicity of two chocolate confections was compared using a rat caries model. One chocolate confection contained 5.6% w/w casein while the other contained 16.6% w/w casein. The levels of fat and sucrose were the same in both confectionery. The casein enrichment was achieved by replacing the 18% w/w non-fat milk solids used normally in the manufacture of milk chocolate with soluble sodium caseinate. Forty Sprague-Dawley male rats infected with streptomycin-resistant Streptococcus mutans consumed the chocolate diets either ad libitum or in a Konig/Hofer programmed feeder. Animals consuming the casein-enriched chocolate either ad libitum or programme-fed had significantly (p < 0.001) lower smooth surface and fissure caries scores than the animals consuming the normal chocolate. There was no significant difference in the mean final body weight, salivary output, or salivary protein, calcium or phosphate concentrations between the animals on the two chocolate diets. There was also no significant difference in the number of total organisms, streptococci or streptomycin-resistant S. mutans recovered from the swabs of the molar teeth of animals on both diets. The work confirms an earlier report of a topical anticariogenic effect of soluble caseinate and shows that it is possible to reduce the cariogenicity of chocolate by caseinate supplementation.
Overexpression of matrix Gla protein mRNA in malignant human breast cells: isolation by differential cDNA hybridization. (1990)

Genetic alterations are involved in the development of human breast cancer. We sought to isolate genes that are differentially expressed or suppressed in cultured human breast carcinoma cells as compared to cultured normal human breast epithelial cells by employing differential screening of selected cDNA libraries. Analysis of several clones thus isolated revealed that the matrix Gla protein (MGP) gene is overexpressed in the breast cancer cell line 600 PEI, though is transcribed at lower levels in most other mammary derived cultures. MGP requires vitamin K dependent gamma-carboxylation for its known function and thus can be inhibited by vitamin K antagonists. This raises the possibility that MGP may be among those factors that when inhibited by vitamin K antagonists reduce metastases in experimental models. Among the gene whose transcription is consistently suppressed upon mammary transformation were fibronectin and the type I keratin, K14. Differential cDNA screening therefore is an effective method of identifying genes involved in various aspects of mammary cell transformation.
Deformation of Progressively Cracking Reinforced Concrete Beams (1984)

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Expression of recombinant human granzyme B. A processing and activation role for dipeptidyl peptidase I. (1995)

Human granzyme B (hGrzB) is the key member of a family of granule serine proteases (granzymes) that participate in target cell death inflicted by cytotoxic lymphocytes. The proenzyme activation peptide predicted from the cDNA encoding hGrzB is composed of two residues. We have devised a PCR strategy to delete this activation dipeptide within hGrzB and express active recombinant hGrzB in mammalian COS cells. Lysates of COS cells transfected with modified hGrzB cDNA were able to hydrolyze tert-butyloxycarbonyl-Ala-Ala-Asp-thiobenzyl ester (Boc-Ala-Ala-Asp-SBzl), whereas lysates transfected with unmodified hGrzB cDNA were inactive. Accordingly, active recombinant hGrzB displayed no significant activities toward substrates containing Met-, Lys-, or Phe- at P1. It has been suggested that the mechanism by which the amino-terminal dipeptide is normally cleaved to generate active GrzB involves dipeptidyl peptidase I (DPPI). Our studies demonstrated that lysates of COS cells cotransfected with unmodified hGrzB cDNA (inactive) and rat DPPI cDNA were able to hydrolyze Boc-Ala-Ala-Asp-SBzl. Similarly, lysates of COS cells transfected with unmodified hGrzB cDNA, and devoid of Asp-ase activity, were also activated upon the addition of bovine spleen DPPI in a pH and time-dependent fashion. These results suggest that the activation dipeptide, and more particularly DPPI, may play and important role in the normal post-translational processing and activation of hGrzB in cytotoxic lymphocytes.
Poly(A)-Attached RNA as Activator in Embryonic Differentiation (1974)

Poly(A)-attached RNA (mRNA) was isolated from chicken and calf hearts. Both mRNAs were found to induce the development of explanted postnodal pieces (PNP) of stage 4 chick blastoderm into beating tubes and/or tissues. Heart formation is specific and the frequency was found to depend entirely upon the concentration of mRNA used. In contrast, the concentration had no influence on other tissue formation e.g., neural tube, tubules, myoblasts, and/or notochord.
Antiviral therapy: current options and challenges. (2000)

This article reviews current options and concepts for drug treatment of viral infections with the exception of human immunodeficiency virus infection. Advances in antiviral drug development and in rapid diagnostic methods have resulted in efficient management strategies, particularly for infections due to herpes simplex virus, varicella-zoster virus, cytomegalovirus, influenza A and B viruses, and chronic hepatitis B and C. Newer antiviral agents, such as valaciclovir and famciclovir, have a high oral bioavailability which permits less frequent intake and avoidance of intravenous therapy in many cases. As an alternative to subcutaneous interferon-alpha (IFN-alpha) treatment, oral lamivudine is now approved for therapy of chronic hepatitis B. The addition of oral ribavirin to IFN-alpha treatment has been shown to be superior to IFN-alpha alone for therapy of chronic hepatitis C. By contrast to amantadine, neuraminidase inhibitors such as zanamivir or oseltamivir (GS4104) have activity against both influenza A and B viruses and are well tolerated. First results of controlled trials with these agents are discussed. The emergence of herpes virus resistance to antiviral drugs is of concern, and validation of alternative treatment for patients with documented resistance is required. Future investigations may also help to clarify the therapeutic role of novel antiviral drugs and formulations, such as the oral prodrug of cidofovir, valganciclovir, compounds 1263W94 and Bay 38-4766, and pleconaril.
Assessment of a PCR technique for the detection and identification ofCryptococcus neoformans (1996)

The 18S ribosomal RNA gene of Cryptococcus neoformans was amplified by polymerase chain reaction (PCR). The primers CPL1 and CPR4 were tested for their ability to amplify DNA from 30 strains of C. neoformans and 27 specimens of cerebrospinal fluid (CSF) from patients with cryptococcal meningitis. A 343 bp product was obtained and its specificity confirmed by Southern hybridization with an internal sequence (INSR4) probe. The sensitivity was 100 fg by Southern analysis and 1 pg using the PCR. Neither human nor a variety of other fungal and bacterial strains (n = 78) gave an amplified product. This PCR method can detect as few as 5 cells ml-1 of C. neoformans in spiked-CSF following a simple processing procedure. The developed system of PCR was more sensitive than the culture method and revealed a very high specificity. The PCR was easy to perform and needed only 4 h for all processes from receiving the CSF to detection of a specific DNA band after agarose gel electrophoresis. This would provide another rapid laboratory method for the diagnosis of cryptococcal meningitis.
Changing the Identity of a tRNA by Introducing a G-U Wobble Pair Near the 3′ Acceptor End (1988)

Although the genetic code for protein was established in the 1960's, the basis for amino acid identity of transfer RNA (tRNA) has remained unknown. To investigate the identity of a tRNA, the nucleotides at three computer-identified positions in tRNAPhe (phenylalanine tRNA) were replaced with the corresponding nucleotides from tRNAAla (alanine tRNA). The identity of the resulting tRNA, when examined as an amber suppressor in Escherichia coli, was that of tRNAAla.
Regional cerebral blood flow and cytokines in young females with fibromyalgia. (2003)

This study shows a significant increase in rCBF of caudate nuclei, a reduction in the pons, some cortical regions activity and a increase in IL 8, IL2r levels of young female patients with FM. These findings are more prominent in patients with low HDRS scores.
Photopolymerization of epoxides. A new type of photopolymerization with photodecomposable silyl ether as coinitiator (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotopolymerization of epoxides. A new type of photopolymerization with photodecomposable silyl ether as coinitiatorShuzi Hayase, Yasunobu Onishi, Shuichi Suzuki, and Moriyasu WadaCite this: Macromolecules 1985, 18, 10, 1799–1804Publication Date (Print):October 1, 1985Publication History Published online1 May 2002Published inissue 1 October 1985https://pubs.acs.org/doi/10.1021/ma00152a002https://doi.org/10.1021/ma00152a002research-articleACS PublicationsRequest reuse permissionsArticle Views175Altmetric-Citations19LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Bcl‐xL mediates increased production of humanized monoclonal antibodies in Chinese hamster ovary cells (2005)

Enhanced product yields, reduction in throughput time, improved cost-effectiveness and product quality are examples of benefits gained by delaying apoptotic cell death in bioreactors. To examine the effect on recombinant protein production, bcl-x(L) was overexpressed in a CHO cell line secreting humanized monoclonal antibody directed against the alpha1beta1 integrin. When cell lines overexpressing bcl-x(L) were compared to the parent, cell viability was increased by 20% and titers by 80%. Total viable cell densities were similar and specific productivities were enhanced by almost two-fold on scale-up to bioreactors. Comparison in a chemically defined media demonstrated an even greater sustained viability in bcl-x(L) expressing cells by 50% and up to 90% increase in titer with no impact on product quality. Caspase 3 activities were monitored as a marker for apoptotic cell death. In the presence of Bcl-x(L), caspase activities were reduced to background levels. The role of Bcl-x(L) in protecting cells from premature death was further examined in studies performed in the presence of NaBu, at concentrations known to trigger cell death. Results demonstrated that cells expressing bcl-x(L) retained 88% cell viability with >2 fold increase in titer. Bcl-x(L) was similarly overexpressed in a different CHO cell line producing a humanized mAb against the chemokine MCP1. Once again, production titer was increased by 80% and viability by 75%. Together the studies have shown that overexpression of bcl-x(L) in production cell lines was able to significantly increase the titer by enhancing both the specific activity and total cell viability while maintaining product quality.