gebhart/patrepeval huggingface dataset:
Adenovirus-Mediated Transfer of Viral IL-10 Gene Inhibits Murine Collagen-Induced Arthritis (1998)

IL-10 is a potent anti-inflammatory cytokine that has received growing attention for its therapeutic potential. We examined the efficiency of adenoviral-mediated gene transfer of IL-10 on the incidence and severity of murine collagen-induced arthritis (CIA). Male DBA1 mice immunized with collagen II were treated by systemic administration of 10(9) plaque-forming units of replication-defective adenoviral vector expressing viral IL-10 (vIL-10) on day 30, when clinical symptoms of arthritis start. The transgene was shown to inhibit the onset of CIA, to decrease severity, and profoundly suppress the overall joint histopathology of the experimental arthritis. Significant IL-10 concentrations were obtained in the serum of injected animals for 7 days. Inhibition of arthritis was enhanced by administration of increasing doses of adenovirus-vIL-10. In addition, the local immunosuppressive effect of gene-delivered vIL-10 could be neutralized by a monoclonal anti-vIL-10 Ab. The CIA symptoms in the group treated with the same construct expressing inactive vIL-10 (vIL-10 mut) were similar to those in untreated animals. Our data indicate that a single systemic administration of an adenoviral vector encoding vIL-10 may be a good candidate to suppress arthritis.
The structure and organization within the membrane of the helices composing the pore-forming domain of Bacillus thuringiensis δ-endotoxin are consistent with an “umbrella-like” structure of the pore (1998)

The aim of this study was to elucidate the mechanism of membrane insertion and the structural organization of pores formed by Bacillus thuringiensis delta-endotoxin. We determined the relative affinities for membranes of peptides corresponding to the seven helices that compose the toxin pore-forming domain, their modes of membrane interaction, their structures within membranes, and their orientations relative to the membrane normal. In addition, we used resonance energy transfer measurements of all possible combinatorial pairs of membrane-bound helices to map the network of interactions between helices in their membrane-bound state. The interaction of the helices with the bilayer membrane was also probed by a Monte Carlo simulation protocol to determine lowest-energy orientations. Our results are consistent with a situation in which helices alpha4 and alpha5 insert into the membrane as a helical hairpin in an antiparallel manner, while the other helices lie on the membrane surface like the ribs of an umbrella (the "umbrella model"). Our results also support the suggestion that alpha7 may serve as a binding sensor to initiate the structural rearrangement of the pore-forming domain.
Nanoscale liposomal formulation of a SYK P-site inhibitor against B-precursor leukemia (2013)

We report preclinical proof of principle for effective treatment of B-precursor acute lymphoblastic leukemia (ALL) by targeting the spleen tyrosine kinase (SYK)-dependent antiapoptotic blast cell survival machinery with a unique nanoscale pharmaceutical composition. This nanoscale liposomal formulation (NLF) contains the pentapeptide mimic 1,4-Bis (9-O dihydroquinidinyl) phthalazine/hydroquinidine 1,4-phathalazinediyl diether (C61) as the first and only selective inhibitor of the substrate binding P-site of SYK. The C61 NLF exhibited a very favorable pharmacokinetic and safety profile in mice, induced apoptosis in primary B-precursor ALL blast cells taken directly from patients as well as in vivo clonogenic ALL xenograft cells, destroyed the in vivo clonogenic fraction of ALL blast cells, and, at nontoxic dose levels, exhibited potent in vivo antileukemic activity against patient-derived ALL cells in xenograft models of aggressive B-precursor ALL. Our findings establish SYK as an attractive molecular target for therapy of B-precursor ALL. Further development of the C61 NLF may provide the foundation for therapeutic innovation against therapy-refractory B-precursor ALL.
Localized photonic nanojets formed by core-shell diffraction gratings (2017)

The generations of localized photonic nanojets using core-shell diffraction gratings working in the visible light region are demonstrated numerically. The power flow patterns for the core-shell diffraction gratings are simulated by using the finite-difference time-domain method. The focusing qualities of localized photonic nanojets are evaluated in terms of focal length and transversal width along propagation and transversal directions. Due to surface plasmon polaritons, it has been demonstrated that the metallic shell is critical for power enhancement of photonic nanojet. The high-resolution imaging of the core-shell diffraction grating can be expected from the high-intensity photonic nanojet. The photonic nanojet could be operated in a wide range imaging for nano-scale targets through the core-shell diffraction grating.
Hybridization in Situ of SV40 Plaques: Detection of Recombinant Sv40 Virus Carrying Specific Sequences of Nonviral DNA (1977)

The detection and recovery of SV40 genomes containing foreign DNA sequences can be facilitated, and the risk of accidental dispersal reduced, by in situ hybridization and radioautography.
ATP interactions of the τ and γ subunits of DNA polymerase III holoenzyme of Escherichia coli (1989)

The tau and gamma subunits of the DNA polymerase III holoenzyme of Escherichia coli were each isolated in large quantities as oligomers from overproducing cells in which their genes (dnaZ and X) were under the control of a T7 phage promoter. The 52-kDa gamma subunit (encoded by the dnaZ sequence) contains three-forths of the N-terminal residues of the 71-kDa tau subunit (encoded by the dnaX sequence). Both gamma and tau share a binding site for ATP (or dATP). A DNA-dependent ATPase activity (Lee, S.H., and Walker, J.R. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 2713-2717) exhibited only by the tau subunit, presumably requires a DNA-binding site in the C-terminal domain lacking in the gamma subunit. Among ATPases dependent on single-stranded DNA, the tau activity is remarkable in the failure of homopolymers (e.g. poly(dA) or poly(dT)) to replace natural DNAs. The presumed need for certain secondary structures may reflect a feature of template binding in the crucial contribution that tau makes to the high processivity of polymerase III holoenzyme. Limited tryptic digestion of tau generates a fragment that resembles gamma in: (i) size, (ii) binding of ATP without ATPase activity, and (iii) a level of complementing holoenzyme activity in extracts of dnaZ-mutant cells that is higher than that of tau.
In vitro inactivation of the rabies virus by ascorbic acid (2003)

These findings suggest that ascorbic acid can be used as an inactivating agent for fixed rabies virus grown in cell culture particularly for the preparation of diagnostic reagents. Further studies are required to evaluate its effect on the cell associated virus, probable therapeutic potential and feasibility of replacing BPL in production of inactivated rabies vaccine.
Detection and Purification of Tyrosine-sulfated Proteins Using a Novel Anti-sulfotyrosine Monoclonal Antibody (2006)

Protein tyrosine O-sulfation is a post-translational modification mediated by one of two Golgi tyrosylprotein sulfotransferases (TPST1 and TPST2) that catalyze the transfer of sulfate to tyrosine residues in secreted and transmembrane proteins. Tyrosine sulfation plays a role in protein-protein interactions in several well defined systems. Although dozens of tyrosine-sulfated proteins are known, many more are likely to exist and await description. Advancing our understanding of the importance of tyrosine sulfation in biological systems requires the development of new tools for the detection and study of tyrosine-sulfated proteins. We have developed a novel anti-sulfotyrosine monoclonal antibody (called PSG2) that binds with high affinity and exquisite specificity to sulfotyrosine residues in peptides and proteins independently of sequence context. We show that it can detect tyrosine-sulfated proteins in complex biological samples and can be used as a probe to assess the role of tyrosine sulfation in protein function. We also demonstrate the utility of PSG2 in the purification of tyrosine-sulfated proteins from crude tissue samples. Finally, Western blot analysis using PSG2 showed that certain sperm/epididymal proteins are undersulfated in Tpst2(-/-) mice. This indicates that TPST1 and TPST2 have distinct macromolecular substrate specificities and provides clues as to the molecular mechanism of the infertility of Tpst2(-/-) males. PSG2 should be widely applicable for identification of tyrosine-sulfated proteins in other systems and organisms.
Expression of a Novel Marine Viral Single-chain Serine Palmitoyltransferase and Construction of Yeast and Mammalian Single-chain Chimera (2006)

The genus Coccolithovirus is a recently discovered group of viruses that infect the globally important marine calcifying microalga Emiliania huxleyi. Surprisingly, the viral genome contains a cluster of putative sphingolipid biosynthetic genes not found in other viral genus. To address the role of these genes in viral pathogenesis, the ehv050 gene predicted to encode a serine palmitoyltransferase (SPT), the first and rate-limiting enzyme of sphingolipid biosynthesis, was expressed and characterized in Saccharomyces cerevisiae. We show that the encoded protein is indeed a fully functional, endoplasmic reticulum-localized, single-chain SPT. In eukaryotes SPT is a heterodimer comprised of long chain base 1 (LCB1) and LCB2 subunits. Sequence alignment and mutational analysis showed that the N-terminal domain of the viral protein most closely resembled the LCB2 subunit and the C-terminal domain most closely resembled the LCB1 subunit. Regardless of whether the viral protein was expressed as a single polypeptide or as two independent domains, it exhibited an unusual preference for myristoyl-CoA rather than palmitoyl-CoA. This preference was reflected by the increased presence of C16-sphingoid bases in yeast cells expressing the viral protein. The occurrence of a single-chain SPT suggested to us that it might be possible to create other fusion SPTs with unique properties. Remarkably, when the two subunits of the yeast SPT were thus expressed, the single-chain chimera was functional and displayed a novel substrate preference. This suggests that expression of other multisubunit membrane proteins as single-chain chimera could provide a powerful approach to the characterization of integral membrane proteins.
A comprehensive approach to flexibility in workflow management systems (1999)

Flexibility has recently grown to be one of the major research topics in the area of workflow management. In this paper we focus on flexibility of workflow management applications, in contrast to flexibility of the implementation of workflow management systems. In a case study we show the necessity of flexibility in workflow management applications. This flexibility can roughly be classified into flexibility, which is provided by the workflow type, and flexibility, which goes beyond the scope of the workflow type and has additionally to be provided by a workflow management system. We call this flexibility by selection and flexibility by adaption, respectively. We point out that the modeling process as a main aspect of flexibility by adaption has to be treated as a CSCW scenario. The classification leads to a structured overall concept for flexibility in workflow management applications.
The Effect of Rosiglitazone on Gluose Metabolism and Insulin Sensitivity in Non Obese Type 2 Diabetic Rat Models (2007)

Background: In Korea, most of type 2 diabetic patients are non obese. We made non obese type 2 diabetic rat models, which were characterized by insulin resistance and insulin secretion defect. Our study aimed to investigate the effect of rosiglitazone on glucose metabolism and insulin sensitivity in non obese type 2 diabetic rat models. Furthermore, we may estimate the effect of rosiglitazone treatment in non obese type 2 diabetic patients in Korea. Methods: 20 male newborn (12 hours old) Sprague-Dawley rats were made diabetes by streptozotocin (75 mg/kg, intraperitoneal injection). At 16 weeks old, diabetes were confirmed by intraperitoneal glucose tolerance test (IPGTT, 30% D/W, 2 kg/kg). After that, diabetic groups were divided into two groups. One group was fed on normal chow and rosiglitazone (3 mg/kg/day) and the other group was fed on normal chow for eight weeks. At the age of 24 weeks, we measured body weight (BW), plasma glucose, insulin, C-peptide levels. And we performed IPGTT and insulin tolerance test (ITT) in two groups. Thereafter, we determined the insulin content of pancreas and epididymal fat weight. Results: Body weight was significantly higher in rosiglitazone group than control group. On IPGTT, plasma glucose, insulin and C-peptide levels were not significantly different between two groups. But, on insulin tolerance test, Kitt (%/min) values of rosiglitazone group were significantly higher than control group (2.7 vs. 1.8). The insulin content of pancreas and epididymal fat weight was not different between two groups. Conclusion: These results suggested that rosiglitazone improved insulin sensitivity in non obese type 2 diabetes rat models independent of glucose level. (J Kor Diabetes Assoc 31:319~325, 2007)
Electrochemical activation of carbon dioxide in ionic liquid: synthesis of cyclic carbonates at mild reaction conditions (2002)

Electrocatalytic cycloaddition of carbon dioxide to epoxides in room temperature ionic liquids as reaction media without any additional supporting electrolyte and catalyst could be conducted with high to excellent performances under mild conditions.
The Structural Basis of G‐Protein‐Coupled Receptor Signaling (Nobel Lecture) (2013)

Cells from different parts of our bodies communicate with each other using chemical messengers in the form of hormones and neurotransmitters. They process information encoded in these chemical messages using G-protein-coupled receptors (GPCRs) located in the plasma membrane. The Nobel Prize for Chemistry 2012 was awarded for studies on GPCRs.
Comparative Analysis of EspF from Enteropathogenic and Enterohemorrhagic Escherichia coli in Alteration of Epithelial Barrier Function (2004)

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are related intestinal pathogens that harbor highly similar pathogenicity islands known as the locus of enterocyte effacement (LEE). Despite their genetic similarity, these two pathogens disrupt epithelial tight junction barrier function with distinct kinetics. EHEC-induced reduction in transepithelial electrical resistance (TER), a measure of barrier function disruption, is significantly slower and more modest in comparison to that induced by EPEC. The variation in bacterial adherence only partially accounted for these differences. The LEE-encoded effector protein EspF has been shown to be critical for EPEC-induced alterations in TER. EspF from both EPEC and EHEC is expressed and secreted upon growth in tissue culture medium. The mutation of EHEC cesF suggested that the optimal expression and secretion of EHEC EspF required its chaperone CesF, as has been shown for EPEC. In contrast to EPEC espF and cesF, mutation of the corresponding EHEC homologs did not dramatically alter the decrease in TER. These differences could possibly be explained by the presence of additional espF-like sequences (designated U- and M-espF, where the letter designations refer to the specific cryptic prophage sequences on the EHEC chromosome closest to the respective genes) in EHEC. Reverse transcription-PCR analyses revealed coordinate regulation of EHEC U-espF and the LEE-encoded espF, with enhanced expression in bacteria grown in Dulbecco-Vogt modified Eagle's medium compared to bacteria grown in Luria broth. Both EHEC espF and U-espF complemented an EPEC espF deletion strain for barrier function alteration. The overexpression of U-espF, but not espF, in wild-type EHEC potentiated the TER response. These studies reveal further similarities and differences in the pathogenesis of EPEC and EHEC.
Base-pair neutral homozygotes can be discriminated by calibrated high-resolution melting of small amplicons (2008)

Genotyping by high-resolution melting analysis of small amplicons is homogeneous and simple. However, this approach can be limited by physical and chemical components of the system that contribute to intersample melting variation. It is challenging for this method to distinguish homozygous G::C from C::G or A::T from T::A base-pair neutral variants, which comprise approximately 16% of all human single nucleotide polymorphisms (SNPs). We used internal oligonucleotide calibrators and custom analysis software to improve small amplicon (42-86 bp) genotyping on the LightScanner. Three G/C (PAH c.1155C>G, CHK2 c.1-3850G>C and candidate gene BX647987 c.261+22,290C>G) and three T/A (CPS1 c.3405-29A>T, OTC c.299-8T>A and MSH2 c.1511-9A>T) human single nucleotide variants were analyzed. Calibration improved homozygote genotyping accuracy from 91.7 to 99.7% across 1105 amplicons from 141 samples for five of the six targets. The average T(m) standard deviations of these targets decreased from 0.067 degrees C before calibration to 0.022 degrees C after calibration. We were unable to generate a small amplicon that could discriminate the BX647987 c.261+22,290C>G (rs1869458) SNP, despite reducing standard deviations from 0.086 degrees C to 0.032 degrees C. Two of the sites contained symmetric nearest neighbors adjacent to the SNPs. Unexpectedly, we were able to distinguish these homozygotes by T(m) even though current nearest neighbor models predict that the two homozygous alleles would be identical.
Combined anti-angiogenic therapy against VEGF and integrin alphabeta in an orthotopic model of ovarian cancer (2009)

Bevacizumab and etaracizumab are more effective in combination than individually in some ovarian cancer models, but not all. Both can sensitize taxane-resistant ovarian cancer cells to paclitaxel, though bevacizumab was superior to etaracizumab in this regard. Further study of this dual anti-angiogenic therapy is warranted.
Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer (1996)

Several DNA-based Sindbis virus vectors were constructed to investigate the feasibility and potential applications for initiating the virus life cycle in cells transfected directly with plasmid DNA. These vectors, when transfected into mammalian cells, have been used to produce virus, to express heterologous genes, and to produce infectious vector particles. This approach involved the conversion of a self-replicating vector RNA (replicon) into a layered DNA-based expression system. The first layer includes a eukaryotic RNA polymerase II expression cassette that initiates nuclear transcription of an RNA which corresponds to the Sindbis virus vector replicon. Following transport of this RNA from the nucleus to the cytoplasm, the second layer, autocatalytic amplification of the vector, proceeds according to the Sindbis virus replication cycle and results in expression of the heterologous gene. The Sindbis virus DNA vectors expressed reporter genes in transfected cells at levels that were comparable to those of in vitro-transcribed RNA replicons and were approximately 10-fold higher than the levels produced by conventional RNA polymerase II-dependent plasmids in which the promoter and reporter gene were linked directly. Reporter gene expression was also observed in rodent muscle following injection with Sindbis virus DNA vectors. In a second application, packaged vector particles were produced in cells cotransfected with complementing replicon and defective helper DNAs. The Sindbis virus-derived DNA vectors described here increase the utility of alphavirus-based vector systems in general and also provide a vector with broad potential applications for genetic immunization.
Studies on Carcinogenesis by Avian Sarcoma Viruses. III. The Differential Effect of Serum and Polyanions on Multiplication of Uninfected and Converted Cells<xref ref-type="fn" rid="FN2">2</xref> (1966)

Infection of chicken embryo cells with avian sarcoma viruses leads to conversion of many properties of the cell. Further studies of factors affecting cell multiplication are reported here. Secondary cultures of chicken embryo fibroblasts were prepared in a growth medium containing serum. After incubation overnight, the cultures were exposed to medium from cultures of uninfected or virus-infected cells and various media were then added. The uninfected and the infected cells were allowed to multiply until they reached the stationary phase, at which time their number was determined (saturation density). It was found that the saturation density was proportional to the amount of serum in the growth medium. When serum was limiting, cultures of converted cells multiplied to a saturation density 50% higher than parallel cultures of uninfected cells. Agar or other polyanions exerted two effects on the saturation density. One was to bind some substance in serum needed for cell multiplication. This substance was used up in cell multiplication and was needed by normal and converted cells. The other was to stimulate multiplication of both uninfected and converted cells. These results lead to the following hypotheses: 1) Multiplication of uninfected and converted cells requires a substance, bound by polyanions, which is present in serum. However, the converted cells require less of this substance per cell division than uninfected cells. 2) Cells produce a toxin bound by polyanions. Converted cells produce more of this toxin than uninfected cells.
Ultrasound: A Chemotherapy Sensitizer (2006)

Chemotherapy plays a very important role in cancer treatment. However, there are still some barriers in the successful use of such therapies, mainly because of the adverse side effects of the anticancer agents and due to the development of chemoresistance. This paper focuses on the use of ultrasound to enhance chemotherapy and to overcome drug resistance. The action of many anticancer agents can be improved with the use of ultrasonic exposure either in vitro or in vivo. Drug resistance can be circumvented using ultrasound alone. Furthermore, the reversal attributable to chemoresistance modifiers, such as verapamil and PSC 833, is augmented by ultrasound. Ultrasound-mediated chemosensitization is usually achieved via increasing intracellular drug accumulation, although other mechanisms are also involved. Ultrasound also can play a role in targeted chemotherapy, releasing anticancer chemicals directly and efficiently into the lesions. However, this promising modality has not been clinically adopted so far and the reasons are discussed.
Isolation of Cryptosporidium Oocysts and Sporozoites Using Discontinuous Sucrose and Isopycnic Percoll Gradients (1987)

Techniques for the large-scale isolation of Cryptosporidium oocysts and sporozoites, obtained from the feces of experimentally infected Holstein calves, were developed employing discontinuous sucrose gradients and isopycnic Percoll gradients. The oocyst recovery method utilized 2 sequential discontinuous sucrose gradients followed by 1 Percoll gradient. Recovered oocysts were essentially free of debris and bacteria and represented 34% of the original oocyst suspension. Sporozoites were recovered from excystation mixtures on a single Percoll gradient. Sixty-three percent of the original sporozoites were recovered with 2.2% contamination by intact oocysts and virtually no oocyst walls.