gebhart/patrepeval huggingface dataset:
Synthesis and Photophysical, Electrochemical, and Electrophosphorescent Properties of a Series of Iridium(III) Complexes Based on Quinoline Derivatives and Different β-Diketonate Ligands (2006)

The synthesis and photophysical, electrochemical, and electrophosphorescent properties of a series of cyclometalated iridium(III) complexes based on quinoline derivatives (C∧N) and different β-diketonate ligands are reported. The iridium complexes contain two quinoline derivatives (C∧N) and a single monoanionic β-diketone (LX), i.e., Ir(C∧N)2(LX), where LX denotes acetylacetonate (acac) or 1-phenyl-3-methyl-4-isobutyryl-5-pyrazolonate (PMIP). Most of the iridium complexes in solution show phosphorescent emission with high quantum efficiencies (0.05−0.25) and microsecond lifetimes (0.5−1.67 μs). The intense phosphorescent emission of these complexes is the result of significant spin−orbit coupling of the iridium center. By modification of the chemical structures of quinoline derivative ligands, the emissive wavelengths of complexes can be tuned from 596 to 634 nm. Interestingly, the photoluminescence quantum efficiency can be improved by the replacement of acac with PMIP. Energy transfer from the hosts poly(9,9-dioctylfluorene) (PFO) and 2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole (PBD) to the guest iridium complex was investigated. Moreover, three iridium complexes were used as dopants to fabricate electrophosphorescent polymer-based light-emitting diodes (PLEDs). The PLEDs show red emission with high external quantum efficiencies, ranging from 7.0 to 9.6%.
Metabolic engineering of acetate-production pathways for the production of isoamyl acetate and succinate in Escherichia coli (2005)

Products derived from the central aerobic metabolic pathway in Escherichia coli often compete with the acetate-producing pathways poxB and ackA-pta for glucose. The production of isoamyl acetate from acetyl-CoA by ATF2, a yeast alcohol acetyltransferase, was a model system to demonstrate the beneficial effects of reducing aerobic acetate production. Ester production was 80% higher in the poxB, ackA-pta strain (0.18 mM) than found in the single ackA-pta mutant, when both overexpressed the PDH complex, panK, and ATF2. Anaerobically, succinate was produced alongside isoamyl acetate to maintain the proper redox balance between NADH and NAD+. The two compounds could be easily separated in an industrial setting because of the difference in their volatilities. An ldhA, adhE double mutant strain served as the control strain to test the effect of an additional ackA-pta mutation. The triple mutant produced 36% more ester (9.4 mM) and 7 times more succinate (45.5 mM) than the control.
Coinfection with Mycoplasma Pneumoniae and Chlamydia Pneumoniae in ruptured plaques associated with acute myocardial infarction (2003)

M. pneumoniae and C. pneumoniae are more frequently found in TRP correlate with the intensity of the inflammation and diameter of the vessel (positive remodeling).
FAP-1: A Protein Tyrosine Phosphatase That Associates with Fas (1995)

Fas is a cell surface receptor that controls a poorly understood signal transduction pathway that leads to cell death by means of apoptosis. A protein tyrosine phosphatase, FAP-1, capable of interacting with the cytosolic domain of Fas, was identified. The carboxyl terminal 15 amino acids of Fas are necessary and sufficient for interaction with FAP-1. FAP-1 expression is highest in tissues and cell lines that are relatively resistant to Fas-mediated cytotoxicity. Gene transfer-mediated elevations in FAP-1 partially abolished Fas-induced apoptosis in a T cell line. These findings are consistent with an inhibitory effect of FAP-1 on Fas signal transduction.
Two E2F Elements Regulate the Proliferating Cell Nuclear Antigen Promoter Differently during Leaf Development (2002)

E2F transcription factors regulate genes expressed at the G1/S boundary of the cell division cycle in higher eukaryotes. Although animal E2F proteins and their target promoters have been studied extensively, little is known about how these factors regulate plant promoters. An earlier study identified two E2F consensus binding sites in the promoter of a Nicotiana benthamiana gene encoding proliferating cell nuclear antigen (PCNA) and showed that the proximal element (E2F2) is required for the full repression of PCNA expression in mature leaves. In this study, we examined the distal element (E2F1) and how it interacts with the E2F2 site to regulate the PCNA promoter. Gel shift assays using plant nuclear extracts or purified Arabidopsis E2F and DP proteins showed that different complexes bind to the two E2F sites. Mutation of the E2F1 site or both sites differentially altered PCNA promoter function in transgenic plants. As reported previously for the E2F2 mutation, the E2F1 and E2F1+2 mutations partially relieved the repression of the PCNA promoter in mature leaves. In young tissues, the E2F1 mutation resulted in a threefold reduction in PCNA promoter activity, whereas the E2F1+2 mutation had no detectable effect. The activity of E2F1+2 mutants was indistinguishable from that of E2F2 mutants. These results demonstrate that both E2F elements contribute to the repression of the PCNA promoter in mature leaves, whereas the E2F1 site counters the repression activity of the E2F2 element in young leaves.
REDUCTION OF CYCLOSPORINE-INDUCED NEPHROTOXICITY BY CILASTATIN FOLLOWING CLINICAL HEART TRANSPLANTATION1 (1994)

The objective of this prospective, randomized, placebo-controlled, single-blinded study in 28 heart-transplanted patients was to investigate whether the dehydropeptidase inhibitor cilastatin reduces cyclosporine-induced nephrotoxicity. Cilastatin is available only in combination with imipenem, a beta-lactam antibiotic to which it is added for reduction of nephrotoxic side-effects of the antimicrobial agent. Patients received either 100 ml placebo (n = 12) or 100 ml (500 mg) imipenem/cilastatin (n = 16) twice perioperatively, and 4 times daily for the first 7 postoperative days. Serum creatinine and urea, as well as urine concentrations of N-acetyl-beta-D-glucosaminidase, which is directly correlated with tubular cell damage, were used as markers for renal function. Thromboxane B2 and 6-keto-prostaglandin F1-alpha serum concentrations were determined to investigate whether there is an imbalance in synthesis of thromboxane A2 and prostacyclin as a possible mechanism for cyclosporine-induced nephrotoxicity. Two placebo patients and 6 patients receiving imipenem/cilastatin had to be excluded from further analysis. Three of 10 placebo patients required hemofiltration, and 2 of them even required hemodialysis, as compared with none in the imipenem/cilastatin group. Creatinine concentrations increased significantly from the second to the fourth postoperative day in the placebo group, but remained nearly normal in cilastatin patients (P < 0.05 for intergroup comparison on postoperative days 2-4). The same trend was observed in urea and N-acetyl-beta-D-glucosaminidase concentrations, without the difference reaching statistical significance. For thromboxane B2 and 6-keto-prostaglandin F1-alpha no differences between the groups could be found. These results suggest that imipenem/cilastatin can counteract acute cyclosporine-induced nephrotoxicity, which appears to be associated with alterations of tubular cell function. The combined use of cyclosporine and imipenem/cilastatin appears to be advantageous in patients following heart transplantation during the initial postoperative period.
Identifying High-Risk Patients with Early-Stage Colon Cancer (2000)

The stage of colon cancer at diagnosis is the most important determinant of prognoses and of chemotherapy decisions. However, accurate staging is
Single chain Ig/γ gene-redirected human T lymphocytes produce cytokines, specifically lyse tumor cells, and recycle lytic capacity (1996)

To enable construction of CTL with known predefined Ab specificity for adoptive immunotherapy, we constructed a chimeric scFv/gamma gene composed of the variable regions of a mAb joined to the Fc(epsilon)RI signaling receptor gamma-chain of mast cells. Introduction of this chimeric receptor into CTL rendered these lymphocytes specific for renal cell carcinoma. This approach combines the specificity of tumor-selective Abs with the efficacy of CTL to destroy tumor cells. We not only demonstrated that the transduced CTL functionally express the scFv/gamma receptor for a prolonged period of time (4.5 mo of in vitro culture), but also showed high levels of Ab-dictated lysis of renal cell carcinoma similar to that of normal CTL, and importantly, we demonstrated that these CTL can recycle their lytic activity. Moreover, these scFv/gamma-expressing T lymphocytes produce cytokines upon stimulation with the relevant target cell. These results together with the donor independence of our gene transduction protocol demonstrate the feasibility of redirecting T lymphocytes for cancer treatment.
Rapid heat-treatment attenuation of infectious bronchitis virus (2010)

In the present study we describe the rapid development of an attenuated live vaccine for GA08, a new serotype of infectious bronchitis virus, using a heat-treatment method. Incubation of the GA08 strain of IBV at 56 degrees C and passage in embryonated eggs was used as a method to fast track the attenuation process. The virus was incubated in a 56 degrees C water bath and aliquots were removed every 5 min for up to 1 h, and then each aliquot was inoculated into 10-day-old embryonated eggs. Virus with the longest incubation time that produced lesions in the embryos was harvested, again incubated at 56 degrees C as described and passaged in embryonated eggs. Attenuation of the virus, designated GA08/GA08HSp16/08, was verified in 1-day-old specific pathogen free chicks. A 10x dose of the vaccine was found to be safe for 2-week-old broiler chicks of commercial origin. The efficacy of the heat-treated attenuated virus was determined by vaccinating broiler chicks of commercial origin at 1 and 14 days of age intraocularly/intranasally. Vaccinated birds that were challenged with 10(4.5) median embryo infectious doses of pathogenic GA08 virus/bird at 28 days of age were protected from the disease, and challenge virus was only detected in the trachea of one of 21 birds by real-time reverse transcriptase-polymerase chain reaction at 5 days post challenge. The attenuation process took 10 weeks to complete, which is a substantially shorter time than required to attenuate infectious bronchitis virus by serial passage in embryonated eggs without heat treatment (38 weeks or more).
Activation of the human complement alternative pathway by Listeria monocytogenes: evidence for direct binding and proteolysis of the C3 component on bacteria (1993)

The capacity of the intracellular pathogen Listeria monocytogenes to activate the alternative pathway of human complement was examined. Incubation of L. monocytogenes with human serum in optimal conditions (20% Mg2+EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid]-chelated serum) consumed (31.3 +/- 3.9)% of C3 hemolytic activity and led to similar amounts of C3 deposition among the 27 strains tested, except for a rough mutant and the penicillin-induced L forms of strain EGD, which bound reduced amounts of C3. The same results were obtained with strains belonging to related species (L. innocua, L. seeligeri, L. welshimeri, and L. ivanovii). Direct evidence is provided that L. monocytogenes induces the deposition of C3b and its cleavage products iC3b and C3d through ester and amide linkages, as demonstrated by the analysis of the released products of radiolabelled purified C3 after treatment with hydroxylamine. Our results clearly demonstrate that L. monocytogenes activates the alternative pathway of human complement, suggesting that bacteria in the blood or in tissues of infected patients are opsonized and targeted to C3 receptor-bearing cells such as macrophages.
The use of Envelope for HIV therapeutics: from vaccines to co-receptors (2000)

The Envelope protein (Env) of the human immunodeficiency virus (HIV) has been a primary target and tool for antiviral drug and vaccine development since the discovery of the virus. The study of Env has led to a knowledge of the virus life-cycle, structure and immunological response that has helped lead HIV-directed therapeutic strategies in new, unexpected directions. In particular, the discovery of chemokine receptors as the HIV co-receptors in 1996 is allowing a new generation of antiviral and vaccine candidates to be developed that are based on the ability to block the function of Env in mediating viral entry. This review discusses the primary roles of Env throughout its course of investigation as a tool for vaccine development and as a target for drug screening, emphasising the recent role of Env in the discovery and exploration of the co-receptors. The use of gp120/chemokine binding assays, chemokine receptor structure-function studies and co-receptor polymorphisms are discussed in the context of the development of high-throughput screening assays, creation of immunogens with enhanced vaccine potential and targeting of the co-receptors CCR5 and CXCR4 by small-molecule inhibitors of HIV entry.
Expression and Purification of Functional Human α-1-Antitrypsin from Cultured Plant Cells (2001)

Human alpha-1-antitrypsin (AAT), the most abundant protease inhibitor found in the blood, was expressed in rice embryonic tissue suspension cell culture. This was accomplished by cloning the codon-optimized AAT gene into a vector containing the rice RAmy3D promoter and its signal sequence. The synthetic gene incorporates codons synonymous with those found in highly expressed rice genes. Approximately 1000 stable transformed calli were produced by particle bombardment mediated transformation and were screened for high AAT expression using a porcine elastase inhibitory activity assay. The band shift assay also confirmed that rice-derived AAT is functional regarding its binding capability to the elastase substrate. Time course studies were conducted to determine the optimum, postinduction expression levels from cell culture. AAT expression equivalent to 20% of the total secreted proteins was achieved, and a purification scheme was developed that yielded active AAT with purity greater than 95%. The potential applications of purified plant-derived AAT for treatments of various AAT-deficient diseases are discussed.
Repression of myogenic differentiation by aFGF, bFGF, and K-FGF is dependent on cellular heparan sulfate. (1992)

We have proposed a model in which fibroblast growth factor (FGF) signalling requires the interaction of FGF with at least two FGF receptors, a heparan sulfate proteoglycan (HSPG) and a tyrosine kinase. Since FGF may be a key mediator of skeletal muscle differentiation, we examined the synthesis of glycosaminoglycans in MM14 skeletal muscle myoblasts and their participation in FGF signalling. Proliferating and differentiated MM14 cells exhibit similar levels of HSPG, while differentiated cells exhibit reduced levels of chondroitin sulfate proteoglycans and heparan sulfate chains. HSPGs, including syndecan, present in proliferating cells bind bFGF, while the majority of chondroitin sulfate and heparan sulfate chains do not. Treatment of skeletal muscle cells with chlorate, a reversible inhibitor of glycosaminoglycan sulfation, was used to examine the requirement of sulfated proteoglycans for FGF signalling. Chlorate treatment reduced glycosaminoglycan sulfation by 90% and binding of FGF to high affinity sites by 80%. Chlorate treatment of MM14 myoblasts abrogated the biological activity of acidic, basic, and Kaposi's sarcoma FGFs resulting in terminal differentiation. Chlorate inhibition of FGF signalling was reversed by the simultaneous addition of sodium sulfate or heparin. Further support for a direct role of heparan sulfate proteoglycans in fibroblast growth factor signal transduction was demonstrated by the ability of heparitinase to inhibit basic FGF binding and biological activity. These results suggest that activation of FGF receptors by acidic, basic or Kaposi's sarcoma FGF requires simultaneous binding to a HSPG and the tyrosine kinase receptor. Skeletal muscle differentiation in vivo may be dependent on FGFs, FGF tyrosine kinase receptors, and HSPGs. The regulation of these molecules may then be expected to have important implications for skeletal muscle development and regeneration.
Enterococcus avium nom. rev., comb. nov.; E. casseliflavus nom. rev., comb. nov.; E. durans nom. rev., comb. nov.; E. gallinarum comb. nov.; and E. malodoratus sp. nov. (1984)

Biochemical, chemical, and genetic data indicate that strains labeled Streptococcus avium (Nowlan and Deibel), “Streptococcus casseliflavus” (Vaughn, Riggsby and Mundt), “Streptococcus durans” (Sherman and Wing), “Streptococcus faecalis subsp. malodoratus” (Pette), and Streptococcus gallinarum (Bridge and Sneath) are closely related to members of the genus Enterococcus Schleifer and Kilpper-Bälz. We propose that these taxa be classified as members of the genus Enterococcus, as Enterococcus avium nom. rev., comb. nov., Enterococcus casseliflavus nom. rev., comb. nov., Enterococcus durans nom. rev., comb. nov., Enterococcus malodoratus sp. nov., and Enterococcus gallinarum comb. nov., respectively.
A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. (2003)

The concept of "field cancerization" was first introduced by Slaughter et al. [D. P, Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular findings support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. In the initial phase, a stem cell acquires genetic alterations and forms a "patch," a clonal unit of altered daughter cells. These patches can be recognized on the basis of mutations in TP53, and have been reported for head and neck, lung, skin, and breast cancer. The conversion of a patch into an expanding field is the next logical and critical step in epithelial carcinogenesis. Additional genetic alterations are required for this step, and by virtue of its growth advantage, a proliferating field gradually displaces the normal mucosa. In the mucosa of the head and neck, as well as the esophagus, such fields have been detected with dimensions of >7 cm in diameter, whereas they are usually not detected by routine diagnostic techniques. Ultimately, clonal divergence leads to the development of one or more tumors within a contiguous field of preneoplastic cells. An important clinical implication is that fields often remain after surgery of the primary tumor and may lead to new cancers, designated presently by clinicians as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding preneoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed.
Conformational analysis of flexible ligands in macromolecular receptor sites (1992)

Abstract A computational method for exploring the orientational and conformational space of a flexible ligand within a macromolecular receptor site is presented. The approach uses a variant of the DOCK algorithm [Kuntz et al., J. Mol. Biol. , 161 , 288 (1982)] to determine orientations of a fragment of the ligand within the site. These positions then form the basis for exploring the conformational space of the rest of the ligand, using a systematic search algorithm. The search incorporates a method by which the ligand conformation can be modified in response to interactions with the receptor. The approach is applied to two test cases, in both of which the crystallographically determined structures are obtained. However, alternative models can also be obtained that differ significantly from those observed experimentally. The ability of a variety of measures of the intermolecular interaction to discriminate among these structures is discussed.
Combination Strategies to Enhance Antitumor ADCC (2012)

The clinical efficacy of monoclonal antibodies as cancer therapeutics is largely dependent upon their ability to target the tumor and induce a functional antitumor immune response. This two-step process of ADCC utilizes the response of innate immune cells to provide antitumor cytotoxicity triggered by the interaction of the Fc portion of the antibody with the Fc receptor on the immune cell. Immunotherapeutics that target NK cells, γδ T cells, macrophages and dendritic cells can, by augmenting the function of the immune response, enhance the antitumor activity of the antibodies. Advantages of such combination strategies include: the application to multiple existing antibodies (even across multiple diseases), the feasibility (from a regulatory perspective) of combining with previously approved agents and the assurance (to physicians and trial participants) that one of the ingredients - the antitumor antibody - has proven efficacy on its own. Here we discuss current strategies, including biologic rationale and clinical results, which enhance ADCC in the following ways: strategies that increase total target-monoclonal antibody-effector binding, strategies that trigger effector cell 'activating' signals and strategies that block effector cell 'inhibitory' signals.
Guessing Random Additive Noise Decoding With Symbol Reliability Information (SRGRAND) (2021)

The design and implementation of error correcting codes has long been informed by two fundamental results: Shannon&#x2019;s 1948 capacity theorem, which established that long codes use noisy channels most efficiently; and Berlekamp, McEliece, and Van Tilborg&#x2019;s 1978 theorem on the NP-completeness of decoding linear codes. These results shifted focus away from creating code-independent decoders, but recent low-latency communication applications necessitate relatively short codes, providing motivation to reconsider the development of universal decoders. We introduce a scheme for employing binarized symbol soft information within Guessing Random Additive Noise Decoding, a universal hard detection decoder. We incorporate codebook-independent quantization of soft information to indicate demodulated symbols to be reliable or unreliable. We introduce two decoding algorithms: one identifies a conditional Maximum Likelihood (ML) decoding; the other either reports a conditional ML decoding or an error. For random codebooks, we present error exponents and asymptotic complexity, and show benefits over hard detection. As empirical illustrations, we compare performance with majority logic decoding of Reed-Muller codes, with Berlekamp-Massey decoding of Bose-Chaudhuri-Hocquenghem codes, with CA-SCL decoding of CA-Polar codes, and establish the performance of Random Linear Codes, which require a universal decoder and offer a broader palette of code sizes and rates than traditional codes.