gebhart/patrepeval huggingface dataset:
Inactivation of the Regulatory Protein B of Soluble Methane Monooxygenase from Methylococcus Capsulatus (Bath) by Proteolysis can be Overcome by a Gly to Gin Modification (1997)

The regulatory protein B of soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath), exists as a mixture of the full-length active form and truncated forms, B' and B". Electrospray ionisation mass spectrometry (ESI-MS) was used to identify a cleavage site between Met12 and Gly13, such that 12 amino acids were lost from the N-terminus of protein B. This truncate was designated B' and molecular masses were assigned to proteins B and B' of 15,852.6+/-0.4 Da and 14,629.5+/-0.3 Da, respectively. A cleavage site between Gln29 and Val30 was also identified such that 29 amino acids were lost from the N-terminus of protein B. This truncate was designated B" and had a molecular mass of 12,709.93+/-0.02 Da. Proteins B' and B" were found to be inactive in the sMMO system. Addition of protease inhibitors or the heterologous expression of protein B in various strains of lon-deficient or ompT-deficient Escherichia coli, did not inhibit B' formation. Expression of protein B as a glutathione S-transferase fusion protein and subsequent purification of protein B from E. coli using affinity chromatography resulted in preparations of protein B with higher enzyme activities than that of wild-type protein B. However, ESI-MS confirmed that protein B' was still present. Alteration of the Met12-Gly13 cleavage site to Met12-Gln13 revealed that the stability of G13Q at 20 degrees C and 37 degrees C was higher than that of wild-type preparations. ESI-MS indicated that protein B' was absent and could only be identified after prolonged incubation at room temperature. The amount of active protein B present in the cell may be controlled by protein B cleavage, thereby regulating electron transfer. Alternatively, it may allow protein B to maintain a certain conformation necessary for enzyme activity and this may control the activity of sMMO in response to the supply of methane to the cell.
Transfer of the human telomerase reverse transcriptase(TERT) gene into T lymphocytes results in extension of replicative potential (2001)

In most human somatic cells telomeres progressively shorten with each cell division eventually leading to chromosomal instability and cell senescence. The loss of telomere repeats with cell divisions may also limit the replicative life span of antigen-specific T lymphocytes. Recent studies have shown that the replicative life span of various primary human cells can be prolonged by induced expression of the telomerase reverse transcriptase (hTERT) gene. To test whether introduction of hTERT can extend the life span of primary human T lymphocytes, naive CD8(+) T lymphocytes were transfected with retroviral vectors containing the hTERT gene. Transduced T-cell clones expressed high levels of telomerase and either maintained or elongated their telomere lengths upon culture for extended periods of time. Two of the transduced subclones retained a normal cloning efficiency for more than 170 population doublings (PDs). In contrast, T-cell clones transfected with control vectors exhibited progressive telomere length shortening and stopped proliferation at around 108 PDs. Telomerase-positive T clones had a normal 46,XY karyotype, maintained their cytotoxic properties, and showed very little staining for the apoptotic marker annexin-V. These results indicate that ectopic hTERT gene expression is capable of extending the replicative life span of primary human CD8(+) cytotoxic T lymphocytes. (Blood. 2001;98:597-603)
Disposition of Phenylbutyrate and its Metabolites, Phenylacetate and Phenylacetylglutamine (1995)

Phenylacetate, an inducer of tumor cytostasis and differentiation, shows promise as a relatively nontoxic antineoplastic agent. Phenylacetate, however, has an unpleasant odor that might limit patient acceptability. Phenylbutyrate, an odorless compound that also has activity in tumor models, is known to undergo rapid conversion to phenylacetate by beta-oxidation in vivo. This phase I study examined the pharmacokinetics of phenylbutyrate and characterized the disposition of the two metabolites, phenylacetate and phenylacetylglutamine. Fourteen patients with cancer (aged 51.8 +/- 13.8 years) received a 30-minute infusion of phenylbutyrate at 3 dose levels (600, 1200, and 2000 mg/m2). Serial blood samples and 24-hour urine collections were obtained. Samples were assayed by high-performance liquid chromatography. A model to simultaneously describe the pharmacokinetics of all three compounds was developed using ADAPT II. Data were modeled as molar equivalents. The model fit the data well as shown by mean (+/- SD) coefficients of determination (r2) for phenylbutyrate, phenylacetate, and phenylacetylglutamine, which were 0.96 +/- 0.07, 0.88 +/- 0.10, and 0.92 +/- 0.06, respectively. The intrapatient coefficient of variation percentage (CV%) around the parameter estimates were small (range 7.2-33.5%). Phenylbutyrate achieved peak concentrations in the range of in vitro tumor activity (500-2000 mumol/L) and exhibited saturable elimination (Km = 34.1 +/- 18.1 micrograms/mL and Vmax = 18.1 +/- 18 mg/h/kg). Metabolism was rapid; the times to maximum concentration for phenylacetate and phenylacetylglutamine were 1 and 2 hours, respectively. The conversion of phenylbutyrate to phenylacetate was extensive (80 +/- 12.6%), but serum concentrations of phenylacetate were low owing to rapid, subsequent conversion to phenylacetylglutamine.(ABSTRACT TRUNCATED AT 250 WORDS)
IL-2-PE40 prevents the development of tumors in mice injected with IL-2 receptor expressing EL4 transfectant tumor cells. (1990)

A number of different immunotherapeutic reagents are currently being developed to target IL-2R for the treatment of leukemia, graft rejection, and certain autoimmune diseases. Previously, we have shown that IL-2-PE40, a chimeric protein composed of human IL-2 linked to the N-terminus of a truncated form of Pseudomonas exotoxin (PE), could effectively kill a variety of cell lines in vitro expressing either low, intermediate, or high affinity IL-2R. Here, we demonstrate that IL-2-PE40 can successfully retard or prevent the growth of a lethal ascites tumor or a solid tumor composed of EL4J murine thymoma cells transfected with the p55 murine IL-2R. The transfected line, EL4J-3.4, expresses 1,000 to 3,000 high affinity IL-2R. Survival extension in the ascites model was achieved by initiating treatment either after 4 to 6 h or within 5 days post-tumor injection in both athymic nude and C57BL/6 mice. Similarly, the growth of an aggressive s.c. solid tumor could also be inhibited. Extension of survival was not achieved either by using the truncated toxin alone not attached to IL-2 or by using an IL-2-PE40Asp553 mutant lacking a functional toxin. Survival extension was not caused by IL-2 activated NK or other host effector mechanisms as IL-2-PE40 was unable to prevent the receptor-negative EL4J parental line from forming a lethal ascites or a solid tumor. Thus, IL-2-PE40 is a potent, specific cytolytic reagent that may prove useful in the arsenal of anti-IL-2R immunotherapeutics.
Voice over IP systems with speech bitrate adaptation based on MPEG-4 wideband CELP (2003)

This paper proposes bitrate adaptation schemes for real-time voice over IP applications, based on multirate and scalable coding capabilities in MPEG-4 CELP. For IP telephony applications, the adaptation scheme based on multi-rate coding is utilized to achieve the best coding quality at a given bitrate. For broadcast applications, the scalable CELP coder produces a layered bitstream and the bitrate control at IP routers determines the number of bitstream layers depending on the network throughputs. Performance evaluation of bitrate adaptation using the MPEG-4 wideband CELP coder is presented.
Coxibs and Cardiovascular Disease (2004)

The coxibs are a subclass of nonsteroidal antiinflammatory drugs (NSAIDs) designed to inhibit selectively cyclooxygenase-2 (COX-2).1 Their development was based on the hypothesis that COX-2 was the source of prostaglandins E2 and I2, which mediate inflammation, and that cyclooxygenase-1 (COX-1) was the source of the same prostaglandins in gastric epithelium, where they afford cytoprotection. Three coxibs — celecoxib, rofecoxib, and valdecoxib — have been approved for use by the Food and Drug Administration (FDA); a fourth, etoricoxib, has been approved by the European regulatory authority, and it and a fifth, lumiracoxib, are currently under consideration for FDA . . .
Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection (2010)

Bacteria producing Klebsiella pneumoniae carbapenemases (KPCs) are rapidly emerging as a cause of multidrug-resistant infections worldwide. Bacterial isolates harbouring these enzymes are capable of hydrolysing a broad spectrum of beta-lactams including the penicillins, cephalosporins, carbapenems and monobactam. Detection of isolates harbouring carbapenemases can be inconsistent using automated systems, often requiring subsequent confirmatory tests. Phenotypic methods utilizing boronic acid disc tests have demonstrated promising results and appear practical for use in clinical microbiology laboratories. Treatment of infection caused by KPC bacteria is particularly worrisome as the carbapenems are often agents of the last resort for resistant Gram-negative infections. The optimal treatment of infections caused by KPC bacteria is not well established and clinical outcome data remain sparse. We reviewed the current literature regarding clinical outcomes following KPC infections, with a specific effort to summarize the clinical data available for specific antimicrobial agents. A total of 15 papers involving 55 unique patient cases were reviewed. While the total number of patients is relatively small, some useful insights could still be gathered to guide clinicians in the management of KPC infections. Tigecycline and the aminoglycosides were associated with positive outcomes in the majority of cases. Clinical success rates were low when the polymyxins were used as monotherapy, but were much higher when they were used in combination. Studies examining combination therapy and well-controlled clinical trials are needed to ascertain the optimal treatment of infections caused by KPC bacteria.
Seamless surface mappings (2015)

We introduce a method for computing seamless bijective mappings between two surface-meshes that interpolates a given set of correspondences. A common approach for computing a map between surfaces is to cut the surfaces to disks, flatten them to the plane, and extract the mapping from the flattenings by composing one flattening with the inverse of the other. So far, a significant drawback in this class of techniques is that the choice of cuts introduces a bias in the computation of the map that often causes visible artifacts and wrong correspondences. In this paper we develop a surface mapping technique that is indifferent to the particular cut choice. This is achieved by a novel type of surface flattenings that encodes this cut-invariance, and when optimized with a suitable energy functional results in a seamless surface-to-surface map. We show the algorithm enables producing high-quality seamless bijective maps for pairs of surfaces with a wide range of shape variability and from a small number of prescribed correspondences. We also used this framework to produce three-way, consistent and seamless mappings for triplets of surfaces.
Transformation ofBacillus thuringiensisvegetative cells by electroporation (1989)

A highly efficient procedure for the transformation of Bacillus thuringiensis and Bacillus subtilis using covalently closed circular plasmid DNA was developed by using the small Staphylococcus aureus plasmid pC194 and electroporation. We have achieved transformation efficiencies in B. thuringiensis subsp. kurstaki (HD-73) greater than 5 x 10(6) transformants/micrograms plasmid DNA. The electro-transformation (or electroporation) procedure also worked with B. subtilis 168 although at a 200-fold less level of efficiency. The results indicated that the plasmid exists in double and single-stranded forms both in B. subtilis and B. thuringiensis. A second single-stranded species was also observed in both species. This technique may prove to be applicable to other members of the genus Bacillus.
Anti-Inflammatory Agents for Cancer Therapy (2009)

Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents.
Normalization of Cholesterol Homeostasis by 2-Hydroxypropyl-β-cyclodextrin in Neurons and Glia from Niemann-Pick C1 (NPC1)-deficient Mice (2012)

Niemann-Pick C (NPC) disease is an inherited, progressive neurodegenerative disorder caused by mutations in the NPC1 or NPC2 gene that result in an accumulation of unesterified cholesterol in late endosomes/lysosomes (LE/L) and impaired export of cholesterol from LE/L to the endoplasmic reticulum (ER). Recent studies demonstrate that administration of cyclodextrin (CD) to Npc1(-/-) mice eliminates cholesterol sequestration in LE/L of many tissues, including the brain, delays neurodegeneration, and increases lifespan of the mice. We have now investigated cholesterol homeostasis in NPC1-deficient cells of the brain in response to CD. Primary cultures of neurons and glial cells from Npc1(-/-) mice were incubated for 24 h with 0.1 to 10 mm CD after which survival and cholesterol homeostasis were monitored. Although 10 mm CD was profoundly neurotoxic, and altered astrocyte morphology, 0.1 and 1 mm CD were not toxic but effectively mobilized stored cholesterol from the LE/L as indicated by filipin staining. However, 0.1 and 1 mm CD altered cholesterol homeostasis in opposite directions. The data suggest that 0.1 mm CD releases cholesterol trapped in LE/L of neurons and astrocytes and increases cholesterol availability at the ER, whereas 1 mm CD primarily extracts cholesterol from the plasma membrane and reduces ER cholesterol. These studies in Npc1(-/-) neurons and astrocytes establish a dose of CD (0.1 mm) that would likely be beneficial in NPC disease. The findings are timely because treatment of NPC disease patients with CD is currently being initiated.
A Commercially Available Dielectric Constant Detector for Liquid Chromatography and Its Applications (1981)

Journal Article A Commercially Available Dielectric Constant Detector for Liquid Chromatography and Its Applications Get access L.V. Benningfield, Jr., L.V. Benningfield, Jr. Applied Automation, Inc., Research, Development,and Engineering Division, Pawhuska Road, Bartlesville, Oklahoma 74004 Search for other works by this author on: Oxford Academic PubMed Google Scholar R.A. Mowery, Jr. R.A. Mowery, Jr. * Applied Automation, Inc., Research, Development,and Engineering Division, Pawhuska Road, Bartlesville, Oklahoma 74004 *Author to whom correspondence should be addressed. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Chromatographic Science, Volume 19, Issue 3, March 1981, Pages 115–123, https://doi.org/10.1093/chromsci/19.3.115 Published: 01 March 1981 Article history Received: 21 May 1980 Revision received: 20 October 1980 Published: 01 March 1981
Immunochemical demonstration of an ovarian cancer‐associated urinary peptide (1982)

Immunization with a peptide fraction from ovarian cancer urine resulted in an antiserum that reacts with a 6,000 dalton (6K) peptide. In urine from some patients with advanced gynaecological cancer, the concentration of 6K peptide was high enough to be detected by immunodiffusion. By radioimmunoassay the levels in normal serum could be determined. The concentrations in serum was 5-20 microgram/l and that in urine 5-50 microgram/l. Elevated levels were observed in urine from 5 out of 8 patients with ovarian cancer, 10 out of 14 patients with cervical cancer and 9 out of 14 patients with endometrial cancer. The highest level observed was 12,000 microgram/l. High concentrations of the 6K peptide (100-300 microgram/l) were observed in amniotic fluid from 14-16 weeks of pregnancy. Some tumor extracts also had a high concentration of the 6K peptide. No immunological relationship was observed between the peptide and known tumor-associated antigens or serum proteins. These results suggest that the peptide is a new oncodevelopmental peptide which may have significance as a tumor marker.
Cellular FLICE-inhibitory protein: an attractive therapeutic target? (2003)

Cellular FLIP (c-FLIP), also known as FLICE-inhibitory protein, has been identified as an inhibitor of apoptosis triggered by engagement of death receptors (DRs) such as Fas or TRAIL (TNF-related apoptosis-inducing ligand). cFLIP is recruited to DR signalling complexes, where it prevents caspase activation. Animal models have indicated that c-FLIP plays an important role in T cell proliferation and heart development. Abnormal c-FLIP expression has been identified in various diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), diabetes mellitus, rheumatoid arthritis (RA) and various cancers. This review focuses on recent insights into c-FLIP dysregulation associated with human diseases and addresses the possibilities of using c-FLIP as a therapeutic target.
Retracted: Epigallocatechin‐3‐Gallate Inhibits Photocarcinogenesis Through Inhibition of Angiogenic Factors and Activation of CD8+ T Cells in Tumors (2005)

There has been considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar UV radiation, including photocarcinogenesis. We and others have shown that topical application of (-)-epigallocatechin-3-gallate (EGCG) from green tea prevents photocarcinogenesis in mice; however, the chemopreventive mechanism of EGCG in an in vivo tumor model is not clearly understood. In this study, UV-B-induced skin tumors with and without treatment of EGCG ( approximately 1 mg/cm(2)) and age-matched skin biopsies from SKH-1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and antitumor immune response using immunostaining, Western blotting and gelatinolytic zymography. We report that compared to non-EGCG-treated tumors, topical application of EGCG in UV-induced tumors resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, which play crucial roles in tumor growth and metastasis. In contrast, tissue inhibitor of MMP-1 (TIMP-1), which inhibits MMP activity, was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors, which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UV-B-induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8(+) T cells) were detected in EGCG-treated tumors compared with non-EGCG-treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity.
Advances in the formation, use and understanding of multi-cellular spheroids (2012)

Multi-cellular spheroids are rich in biological content and mimic better the in vivo environment than 2D cell culture. New technologies to form and analyze spheroids are rapidly increasing their adoption and expanding their applications.
Structural Variety of Membrane Permeable Peptides (2003)

Peptide-mediated protein delivery into living cells has been attracting our attention. Among the peptides that have been reported to have carrier activity, the one from the human immunodeficient virus (HIV)-1 Tat has been most often used for the introduction of exogenous macromolecules into cells. We have shown that not only the Tat peptide, but also various arginine-rich peptides showed very similar characteristics in translocation, and the possible presence of ubiquitous internalization mechanisms among the arginine-rich peptides has also been suggested. These arginine-rich peptides includes ones derived from HIV-1 Rev and flock house virus coat proteins. The linear- and branched-chain peptides containing approximately 8 residues of arginine also show a similar ability. In this review, we present the structural variety of membrane permeable peptides and provide a survey of the findings on the translocation of these peptides through the cell membranes.
Colloidal superlattices for unnaturally high-index metamaterials at broadband optical frequencies (2015)

The recent advance in the assembly of metallic nanoparticles (NPs) has enabled sophisticated engineering of unprecedented light-matter interaction at the optical domain. In this work, I expand the design flexibility of NP optical metamaterial to push the upper limit of accessible refractive index to the unnaturally high regime. The precise control over the geometrical parameters of NP superlattice monolayer conferred the dramatic increase in electric resonance and related effective permittivity far beyond the naturally accessible regime. Simultaneously, effective permeability change, another key factor to achieving high refractive index, was effectively suppressed by reducing the thickness of NPs. By establishing this design rule, I have achieved unnaturally high refractive index (15.7 at the electric resonance and 7.3 at the quasi-static limit) at broadband optical frequencies (100 THz ~300 THz). I also combined this NP metamaterial with graphene to electrically control the high refractive index over the broad optical frequencies.
Development of a Miniaturized Fiber-optic LDV Sensor for Local Blood Velocity Measurement (2013)

A novel, less invasive, miniaturized fiber-optic laser Doppler velocimetry (LDV) sensor, which can be directly inserted into a blood vessel was developed for clinical use in measurements of local blood velocity. A convex lens-like surface was formed by a chemical etching on the fiber's tip that had a core diameter of 50 m. A laser beam that was emitted from the fiber's tip was focused and formed the measuring volume. This fiber sensor was inserted at an insertion angle of 60 through an injection needle, into the flow duct of an acrylic pipe in which highly concentrated fluid, such as whole blood, was flowing in a pulsatile manner. The flow was modeled after human middle cerebral arterial flow. In this study, the local flow velocity and velocity profile across the duct were measured in the pulsatile flow of a dense suspension of a white pigment. The results were compared both with the results obtained using a fringe-mode LDV and with the results that were calculated on the basis of Womersley's oscillatory flow theory. Consequently, it was found that the local velocity and its profile in the pulsatile flow can be successfully measured using the present fiber-optic LDV sensor, which proved the capability of the sensor as a diagnostic device.