gebhart/patrepeval huggingface dataset:
Rational Conversion of Substrate and Product Specificity in a Salvia Monoterpene Synthase: Structural Insights into the Evolution of Terpene Synthase Function (2007)

Terpene synthases are responsible for the biosynthesis of the complex chemical defense arsenal of plants and microorganisms. How do these enzymes, which all appear to share a common terpene synthase fold, specify the many different products made almost entirely from one of only three substrates? Elucidation of the structure of 1,8-cineole synthase from Salvia fruticosa (Sf-CinS1) combined with analysis of functional and phylogenetic relationships of enzymes within Salvia species identified active-site residues responsible for product specificity. Thus, Sf-CinS1 was successfully converted to a sabinene synthase with a minimum number of rationally predicted substitutions, while identification of the Asn side chain essential for water activation introduced 1,8-cineole and alpha-terpineol activity to Salvia pomifera sabinene synthase. A major contribution to product specificity in Sf-CinS1 appears to come from a local deformation within one of the helices forming the active site. This deformation is observed in all other mono- or sesquiterpene structures available, pointing to a conserved mechanism. Moreover, a single amino acid substitution enlarged the active-site cavity enough to accommodate the larger farnesyl pyrophosphate substrate and led to the efficient synthesis of sesquiterpenes, while alternate single substitutions of this critical amino acid yielded five additional terpene synthases.
Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells. (1992)

A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (ch14.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor-infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than that of the native chimeric antibody. The ability of resting 660 TIL cells to kill their autologous GD2-positive target cells was enhanced if the target cells were first coated with the fusion protein. This stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2. Such antibody-cytokine fusion proteins may prove useful in targeting the biological effect of IL2 and other cytokines to tumor cells and in this way stimulate their immune destruction.
Chimeric Antigen Receptor Therapy for B-cell Malignancies (2011)

We presented data showing that the CART-19 cells expressing the 4-1BB signaling domain can have unprecedented and massive in-vivo expansion, traffic to tumor sites, persist long term in vivo, and induce rapid and potent anti-tumor activity in chemotherapy refractory CLL patients.
Heat shock protein response in a prostate tumor model to interstitial thermotherapy: Implications for clinical treatment (1993)

Hyperthermia is being utilized individually and in conjunction with other therapies in treating malignant and benign tumors, though few studies have examined cellular effects of elevated temperatures in the prostate model. Highly conserved proteins of the 70 kDa heat shock protein family (HSP 70) are produced in response to environmental stresses, including heat, and are found in all organisms. HSPs are an indicator of cell damage, are associated with thermotolerance, and provide cells with transient resistance to subsequent thermal challenges. Transient thermotolerance is important in the determination of temperature, duration, and sequencing for treatments. This preliminary study analyzes the HSP 70 response of the Dunning R3327 adenocarcinoma model to a single 50 degrees C 1 hr treatment. Elevated HSP levels were found between 10 and 16 hr, returning to baseline by 24 hr. As some fractions of the cells are able to produce HSP 70 following treatment, the data suggest that currently utilized clinical temperatures (42-46 degrees C) administered for 1 hr are inadequate. HSP levels in response to hyperthermia, radiation, and chemotherapy may be useful in finding optimal treatment regimens for prostate cancer.
Targeting the HUβ Protein Prevents Porphyromonas gingivalis from Entering into Preexisting Biofilms (2018)

The oral cavity is home to a wide variety of bacterial species, both commensal, such as various streptococcal species, and pathogenic, such as <i>Porphyromonas gingivalis</i>, one of the main etiological agents of periodontal disease. Our understanding of how these bacteria ultimately cause disease is highly dependent upon understanding how they coexist and interact with one another in biofilm communities and the mechanisms by which biofilms are formed. Our research has demonstrated that the DNABII family of DNA-binding proteins are important components of the extracellular DNA (eDNA)-dependent matrix of bacterial biofilms and that sequestering these proteins via protein-specific antibodies results in the collapse of the biofilm structure and release of the resident bacteria. While the high degree of similarity among the DNABII family of proteins has allowed antibodies derived against specific DNABII proteins to disrupt biofilms formed by a wide range of bacterial pathogens, the DNABII proteins of <i>P. gingivalis</i> have proven to be antigenically distinct, allowing us to determine if we can use anti-<i>P. gingivalis</i> HUβ antibodies to specifically target this species for removal from a mixed-species biofilm. Importantly, despite forming homotypic biofilms <i>in vitro</i>, <i>P. gingivalis</i> must enter preexisting biofilms <i>in vivo</i> in order to persist within the oral cavity. The data presented here indicate that antibodies derived against the <i>P. gingivalis</i> DNABII protein, HUβ, reduce by half the amount of <i>P. gingivalis</i> organisms entering into preexisting biofilm formed by four oral streptococcal species. These results support our efforts to develop methods for preventing and treating periodontal disease.<b>IMPORTANCE</b> Periodontitis is one of the most prevalent chronic infections, affecting 40 to 50% of the population of the United States. The root cause of periodontitis is the presence of bacterial biofilms within the gingival space, with <i>Porphyromonas gingivalis</i> being strongly associated with the development of the disease. Periodontitis also increases the risk of secondary conditions and infections such as atherosclerosis and infective endocarditis caused by oral streptococci. To induce periodontitis, <i>P. gingivalis</i> needs to incorporate into preformed biofilms, with oral streptococci being important binding partners. Our research demonstrates that targeting DNABII proteins with an antibody disperses oral streptococcus biofilm and prevents <i>P. gingivalis</i> entry into oral streptococcus biofilm. These results suggest potential therapeutic treatments for endocarditis caused by streptococci as well as periodontitis.
Immunochemical and Molecular Genetic Analysis of Bacterial Pathogens (1988)

Preface. List of contributors. TOPICAL REVIEW SECTION Chapter 1: Flagella: their role in virulence (C.J. Smyth). Chapter 2: Fimbriae: their role in virulence (C.J. Smyth). Chapter 3: Outer membrane proteins: their role in virulence (P. Owen). Chapter 4: Extracellular toxins: their role in virulence (J.P. Arbuthnott). Chapter 5: Surface antigens of Bordetella pertussis: their role in virulence (J.H. Freer). Chapter 6: Genetic analysis of pathogenesis of enteric bacteria (R. Curtiss III, A.T. Maurelli and P.A. Gulig). Chapter 7: Cholera, the cholera enterotoxins, and the cholera enterotoxin-related enterotoxin family (R.A. Finkelstein). Chapter 8: Genetic analysis of Staphylococcus aureus virulence (T.J. Foster, P.W. O'Toole and M. O'Reilly). Chapter 9: Analysis of virulence of Treponema pallidum: the pathology and immunology of experimental syphilis (M.J. Bailey, A. Cockayne and C.W. Penn). Chapter 10: Surface antigens of Pseudomonas aeruginosa: analysis by crossed immunoelectrophoresis and role in protection (S. MacIntyre, T. McVeigh and P. Owen). Chapter 11: Strategies in bacterial vaccine development (D.J. Maskell and G. Dougan). Chapter 12: Animal models in the study of pathogenesis (C. Adlam). METHODS SECTION Chapter 13: Construction of gene libraries in bacteriophage lambda vectors (P. O'Toole and T.J. Foster). Chapter 14: Screening lambda libraries and detection of recombinants (M. O'Reilly, P. O'Toole and T.J. Foster). Chapter 15: Transformation of bacterial protoplasts (M. O'Reilly and T.J. Forster). Chapter 16: Production of monoclonal antibodies for studies of bacterial virulence (A. McHale and R.J. Russell). Chapter 17: Assays for fimbrial adhesins (C.J. Smyth). Chapter 18: Crossed immunoelectrophoresis: a literature guide (P. Owen). Chapter 19: Western immunoblotting (P. Caffrey, T. McVeigh and P. Owen). Chapter 20: Silver staining of proteins and lipopolysaccharides in SDS-polyacrylamide gels (T. McVeigh, P. Caffrey and P. Owen). Chapter 21: Purification of Staphylococcal exotoxins (J.C.S. De Azavedo and J.P. Arbuthnott). Chapter 22: Detection of extracellular toxins (J.C.S. De Azavedo and J.P. Arbuthnott).Chapter 23: An in vitro method for the study of leucocyte migration inhibition (R.J. Russell). Chapter 24: A simple method of bacterial characteristics and growth in vitro (J.C.S. De Azavedo and R.J. Russell). Chapter 25: Animal requirements in the study of bacterial pathogenesis (P. Nowlan). Subject Index.
Metformin Decreases Food Consumption and Induces Weight Loss in Subjects with Obesity with Type II Non‐Insulin‐Dependent Diabetes (1998)

Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased food intake. This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss. Twelve diet-treated NIDDM women with obesity were randomly given two dose levels (850 mg or 1700 mg) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3x3 Latin square design. The number of sandwich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake, and the level of subjective hunger was rated just before the sandwich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast. The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment. The 1700-mg metformin dose had the most marked appetite suppressant action. Similarly, hunger ratings were significantly lowered after metformin, and the effect was most pronounced after the administration of 1700 mg of metformin. To assess the efficacy of metformin in reducing bodyweight, 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA (American Diabetes Association) diet before being randomized to receive either metformin (850 mg) or placebo twice daily in a double-blind fashion for 24 weeks. A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period. Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment; their mean maximum weight loss was 8 kg greater than that of the placebo group, with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period. These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity.
Multireplicon genome architecture of Lactobacillus salivarius (2006)

Lactobacillus salivarius subsp. salivarius strain UCC118 is a bacteriocin-producing strain with probiotic characteristics. The 2.13-Mb genome was shown by sequencing to comprise a 1.83 Mb chromosome, a 242-kb megaplasmid (pMP118), and two smaller plasmids. Megaplasmids previously have not been characterized in lactic acid bacteria or intestinal lactobacilli. Annotation of the genome sequence indicated an intermediate level of auxotrophy compared with other sequenced lactobacilli. No single-copy essential genes were located on the megaplasmid. However, contingency amino acid metabolism genes and carbohydrate utilization genes, including two genes for completion of the pentose phosphate pathway, were megaplasmid encoded. The megaplasmid also harbored genes for the Abp118 bacteriocin, a bile salt hydrolase, a presumptive conjugation locus, and other genes potentially relevant for probiotic properties. Two subspecies of L. salivarius are recognized, salivarius and salicinius, and we detected megaplasmids in both subspecies by pulsed-field gel electrophoresis of sizes ranging from 100 kb to 380 kb. The discovery of megaplasmids of widely varying size in L. salivarius suggests a possible mechanism for genome expansion or contraction to adapt to different environments.
The application of module in Logistics Management Information System (LSMIS) (2005)

With the limit of compiling environment, the beans technique before couldn't meet the requirement of improving reusing, maintenance and multi-platform used of software. This paper introduces the design of the function level in system structure based on the Web and the application in Logistics Management System. The level consists of some JavaBeans that can be transplanted, reused, replaced and complete the system functions through calling each other.
Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis. (1989)

We have previously experimentally analyzed the structural requirements for interaction between peptide antigens and mouse major histocompatibility complex (MHC) molecules of the d haplotype. We describe here two procedures devised to predict specifically the capacity of peptide molecules to interact with these MHC class II molecules (IAd and IEd). The accuracy of these procedures has been tested on a large panel of synthetic peptides of eukaryotic, prokaryotic, and viral origin, and also on a set of overlapping peptides encompassing the entire staphylococcal nuclease molecule. For both sets of peptides, IAd and IEd binding was successfully predicted in approximately 75% of the cases. This suggests that definition of such sequence "motifs" could be of general use in predicting potentially immunogenic peptide regions within proteins.
Compartmental modeling with nitrogen-15 to determine effects of degree of fat saturation on intraruminal N recycling. (2000)

Two- and three-compartment models were developed to describe N kinetics within the rumen using three Holstein heifers and one nonlactating Holstein cow fitted with ruminal and duodenal cannulas. A 4 x 4 Latin square design included a control diet containing no supplemental fat and diets containing 4.85% of diet dry matter as partially hydrogenated tallow (iodine value = 13), tallow (iodine value = 51), or animal-vegetable fat (iodine value = 110). Effects of fat on intraruminal N recycling and relationships between intraruminal N recycling and ruminal protozoa concentration or the efficiency of microbial protein synthesis were determined. A pulse dose of 15(NH4)2SO4 was introduced into the ruminal NH3 N pool, and samples were taken over time from the ruminal NH3 N and nonammonia N pools. For the three-compartment model, precipitates of nonammonia N after trichloroacetic acid and ethanol extraction were defined as slowly turning over nonammonia N; rapidly turning over nonammonia N was determined by difference. Curves of 15N enrichment were fit to models with two (NH3 N and nonammonia N) or three (NH3 N, rapidly turning over nonammonia N, and slowly turning over nonammonia N) compartments using the software SAAM II. Because the three-compartment model did not remove a small systematic bias or improve the fit of the data, the two-compartment model was used to provide measurements of intraruminal N recycling. Intraruminal NH3 N recycling (45% for control) decreased linearly as fat unsaturation increased (50.2, 43.0, and 41.7% for partially hydrogenated tallow, tallow, and animal-vegetable fat, respectively). Intraruminal nitrogen recycling was not correlated with efficiency of microbial protein synthesis or ruminal protozoa counts.
Novel concepts for injection lasers (2002)

Modern trends in the design of semiconductor lasers are ad- dressed. Nanoscale coherent inclusions of a narrower bandgap semi- conductor in a wider gap semiconductor matrix, or quantum dots (QDs), are designed as a new type of active medium for injection lasers. QDs provide a possibility to extend the wavelength range of heterostructure lasers on GaAs substrates to 1.3 mm and beyond and improve their device performance. We realize 330-mW cw 1.3-mm single-mode con- tinuous wave edge emitters and 1.2-mW cw vertical-cavity surface- emitting lasers (VCSELs). Long operation lifetimes and other competitive device parameters are demonstrated. Novel device designs are pro- posed. In one concept, high-order mode filtering in structures with peri- odically modulated refractive index containing a ''defect'' enables realiza- tion of stable narrow-beam divergence fundamental mode lasing in both edge emitters and VCSELs. In a different novel design, light propagates at some angle with respect to multilayer interference reflectors (MIRs), and the MIRs and the cavity are calculated for the tilted photon inci- dence. A ''tilted cavity'' laser (TCL) gives wavelength-stabilized operation in edge and (or) in surface direction and does not require materials hav- ing a high refractive index difference. New generations of semiconductor optical amplifiers, photodetectors, optical fibers, etc. may become a re- ality. © 2002 Society of Photo-Optical Instrumentation Engineers.
Identification of a telomere-binding activity from yeast. (1986)

In yeast, the ends of the chromosomes (telomeres) terminate in repeated poly(C1-3A) sequences. We have identified a yeast activity that binds specifically to these poly(C1-3A) repeats. An agarose gel binding assay was used to detect and characterize this activity in cell extracts using both cloned telomere DNA and yeast genomic DNA as substrates. The activity appears to bind specifically to poly(C1-3A) sequences, despite their different primary sequences, yet does not bind specifically to telomeric repeats, such as poly(C4A2), poly(C4A4), and poly (C1-8T) from other lower eukaryotes.
Psychosocial Resolution and Counsellor Trainee Empathy. (1992)

New triplet chemotherapy combinations are under investigation in advanced non small cell lung cancer (NSCLC). Carboplatin, plus paclitaxel, plus gemcitabine is among the most active and promising regimens. The use of more aggressive chemotherapy in order to improve results can increase toxicity. Amifostine (WR-2721) reduces toxicity of radiotherapy and chemotherapy and protects selectively a number of normal, but not neoplastic, tissue. Based on this background, we performed a phase II study on carboplatin, plus paclitaxel, plus gemcitabine with amifostine support in advanced NSCLC. Patients received chemotherapy at the following dosage: carboplatin AUC 5, i.v., at day 1; paclitaxel 175 mg/m2, i.v. by 3-hour infusion, at day 1; gemcitabine 1000 mg/m2, i.v. by 3-hour infusion, at days 1 and 8; every 3 weeks for a maximum of 6 cycles. Amifostine was administered at the dose of 740 mg/m2, i.v., at day 1 of each cycle. Seventeen patients entered the study. They were prevalently male, median age was 62 years, PS (ECOG) was 0 in 10 cases (58.8%), 1 in 6 (35.3%) and 2 in 1 (5.9%). Histology was epidermoid in 8 cases (47%) and adenocarcinoma in 9 (53%). We observed 8 (47.5%) objective responses with 2 (11.7%) complete responses. Median time to progression and median survival were 24 and 36 weeks, respectively. Treatment was well tolerated. The main toxicity was as follows: grade 3 neutropenia, grade 2 thrombocytopenia and grade 3 anemia in one (5.8%) case; grade 2 peripheral neurologic toxicity in 3 (17.6%) patients; grade 2 cardiac toxicity (atrial fibrillation) in one case; and grade 3 respiratory toxicity (dispnoea) in one patient. These data indicate that this combination has promising activity and tolerability. A randomized trial comparing carboplatin plus paclitaxel, plus gemcitabine versus carboplatin, plus paclitaxel, plus gemcitabine, plus amifostine in advanced NSCLC is warranted.
Synthesis of 2-deoxy-2,2-difluoro-D-ribose and 2-deoxy-2,2'-difluoro-D-ribofuranosyl nucleosides (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 2-deoxy-2,2-difluoro-D-ribose and 2-deoxy-2,2'-difluoro-D-ribofuranosyl nucleosidesL. W. Hertel, J. S. Kroin, J. W. Misner, and J. M. TustinCite this: J. Org. Chem. 1988, 53, 11, 2406–2409Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/jo00246a002https://doi.org/10.1021/jo00246a002research-articleACS PublicationsRequest reuse permissionsArticle Views3009Altmetric-Citations317LEARN 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
Identification of Marek's disease virus nuclear antigen in latently infected lymphoblastoid cells (1988)

A new Marek's disease virus (MDV) nuclear antigen (MDNA) was identified in two MDV-transformed T-lymphoblastoid cell lines, MKT-1 and MSB-1, derived from chickens bearing tumors induced by MDV. This MDNA was not detected in MSB-1 cells maintained in iododeoxyuridine, which activates the latent MDV genome. Moreover, it was not found in chicken embryo fibroblasts undergoing productive and cytolytic infection with MDV. Expression of MDNA is not related to strain pathogenicity in chickens, because chicken embryo fibroblasts productively infected with the pathogenic RBIB strain or the nonpathogenic CV-1 strain of MDV did not express this antigen. DNA-protein immunoprecipitation studies revealed that MDNA bound to two sites in the 190,00-base-pair (bp) MDV genome. One of these loci identified by MDNA obtained from MKT-1 and MSB-1 cells corresponded to a 476-bp segment within the short unique region of BamHI-A MDV DNA. A second locus located in a 280-bp segment within the short inverted repeat region of BamHI-A was also identified by MDNA from MSB-1 cells but not by MDNA obtained from MKT-1 cells. Analyses of the nucleotide sequence by DNase digestion showed that MDNA protected a 60-bp segment spanning a 22-bp palindromic sequence of the short unique region and a 103-bp sequence encompassing a 32-bp palindrome in the short inverted repeat region of BamHI-A MDV DNA.