gebhart/patrepeval huggingface dataset:
Fusidilactones, a New Group of Polycyclic Lactones from an Endophyte, Fusidium sp. (2002)

The bicyclic fusidilactones A (1) and B (2) and the structurally unusual fusidilactone C (4) with an oxoadamantane skeleton, a spiro acetal structure and two ether-bridged hemiacetals were isolated from the fungal endophyte Fusidium sp. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
Prevention with sucralfate gel of NSAID-induced gastroduodenal damage in arthritic patients. (1996)

Sucralfate gel reduces both the incidence of acute gastroduodenal mucosal lesions and symptoms in patients with arthritis receiving short-term nonsteroidal anti-inflammatory drugs.
Potentiation of chlorambucil cytotoxicity in B-cell chronic lymphocytic leukemia by inhibition of DNA-dependent protein kinase activity using wortmannin. (1998)

In this study, we examined the ability of wortmannin to modulate chlorambucil (CLB) cytotoxicity in lymphocyte samples from patients with B-cell chronic lymphocytic leukemia (B-CLL). It has been suggested previously that enhanced cross-link repair is a primary mechanism of resistance to nitrogen mustards (NMs) in B-CLL. DNA-dependent protein kinase (DNA-PK) is involved in the repair of double-strand breaks and in rejoining steps in recombination mechanisms. Mutants defective in this process are hypersensitive to alkylating agents. We have recently demonstrated that the activity of DNA-PK is a determinant in the cellular response of B-CLL to CLB. The DNA-PK gene has homology to the P110 phosphatidylinositol 3-kinase (PI 3-K). Wortmannin, an inhibitor of P110 PI 3-K, also inhibits DNA-PK activity in vitro. We investigated the effect of wortmannin on DNA-PK activity and CLB toxicity in the lymphocytes from 11 patients with B-CLL. Our results demonstrate that DNA-PK activity is decreased after exposure to wortmannin in a dose-dependent manner. Wortmannin, at nontoxic concentrations, synergistically sensitized B-CLL lymphocytes to the effects of CLB. Moreover, we observed a significant correlation when we compared the fold decrease in DNA-PK activity and the synergistic value (I), obtained when wortmannin was used at 0.1 microM. In the resistant B-CLL lymphocyte samples, there was a highly significant correlation between the ability of wortmannin at 0.1 and 0.25 microM to decrease the level of DNA-PK activity and to increase CLB sensitivity. In a model of primary human tumor cells, our findings suggest that the inhibition of DNA-PK activity may be a powerful way to overcome resistance to NMs such as CLB and point to new possibilities to improve the effectiveness of NM therapy.
CA125 suppresses amatuximab immune-effector function and elevated serum levels are associated with reduced clinical response in first line mesothelioma patients (2018)

The tumor-shed antigen CA125 has recently been found to bind certain monoclonal antibodies (mAbs) and suppress immune-effector mediated killing through perturbation of the Fc domain with CD16a and CD32a Fc-γ activating receptors on immune-effector cells. Amatuximab is a mAb targeting mesothelin whose mechanism of action utilizes in part antibody-dependent cellular cytotoxicity (ADCC). It is being tested for its therapeutic activity in patients with mesothelioma in combination with first line standard-of-care. To determine if CA125 has immunosuppressive effects on amatuximab ADCC and associated clinical outcomes, post hoc subgroup analysis of patients from a Phase 2 study with primary diagnosed stage III/IV unresectable mesothelioma treated with amatuximab plus cisplatin and pemetrexed were conducted. Analysis found patients with baseline CA125 levels no greater than 57 U/m (∼3X the upper limit of normal) had a 2 month improvement in progression free survival (HR = 0.43, p = 0.0062) and a 7 month improvement in overall survival (HR = 0.40, p = 0.0022) as compared to those with CA125 above 57 U/mL. In vitro studies found that CA125 was able to bind amatuximab and perturb ADCC activity via decreased Fc-γ-receptor engagement. These data suggest that clinical trial designs of antibody-based drugs in cancers producing CA125, including mesothelioma, should consider stratifying patients on baseline CA125 levels for mAbs that are experimentally determined to be bound by CA125.
Liver cell-mediated alleviation of acute ischemic myocardial injury (2010)

Cardiomyocyte injury occurs in myocardial ischemia, resulting in impairment of cardiac function. As the endogenous protective function of adult cardiomyocytes is limited, nonmyocytic cells may be activated to protect myocardium from ischemic injury. In this investigation, we demonstrated in a mouse model of myocardial ischemia that the liver was able to respond to myocardial ischemia to upregulate a number of genes encoding secreted proteins, mobilize its cells, and release cell contents into the circulatory system. These naturally occurring mechanisms suggested a possible cardioprotective role for myocardial ischemia-conditioned liver cells and inspired us to develop cardioprotective therapies based on these mechanisms. We demonstrated that administration of liver cell extract derived from myocardial ischemic mice, but not sham control mice, resulted in a significant reduction in acute myocardial infarction as well as the density of TUNEL+ cells in ischemic myocardium compared to administration of PBS at 2, 6, 12, and 24 hrs. These observations suggest that liver cells may respond to myocardial ischemia to express cardioprotective factors, which may be identified and used for alleviating myocardial infarction.
Determination of T-2 toxin in feed by high performance liquid chromatography with fluorescence detection after immunoaffinity column purification (2013)

A method of determining T-2 toxin in feed was established by high performance liquid chromatography with fluorescence detection via immunoaffinity column purification and precolumn derivatization.A sample was extracted with methanol-water(V/V= 80/20),purified by immunoaffinity columns containing antibodies specific for T-2 toxin,and quantified by reversed phase high performance liquid chromatography with fluorescence detection after derivatization with 1-anthroylnitrile(1- AN)and 4-dimethylam inopyridine(DMAP).The results showed that the linearity range of T-2 toxin was 10～200μg/L,the recovery was 76.9%～92.l%,and the relative standard deviation was under 6%,indicating that this method could precisely determine T-2 toxin in feed.
Tuberculosis vaccines: the past, present and future (2002)

Tuberculosis still remains a leading infectious cause of death worldwide, although the BCG vaccine has been used for 80 years. There is an urgent need to develop improved BCG or new tuberculosis vaccines. This apparently represents a daunting task, since it will take a long time before a vaccine can be declared to be better than the current BCG vaccine, both in experimental and human studies. The current review takes a brief historic look at the use of current BCG vaccine and provides an overview on what are considered to be the key immunologic criteria that have to be met by a new generation of tuberculosis vaccines. It also provides the most up-to-date information on the latest developments in tuberculosis vaccine research, with a focus on mycobacterial organism-based and Mycobacterium tuberculosis antigen-based vaccines. Consideration is also given to the mucosal route of immunization and 'prime and boost' regimens. This review also presents several important tables, highlighting critical components of antituberculosis immunity, the most commonly tested immune adjuvants, the types of novel tuberculosis antigen-based vaccines and the outcome of different heterologous 'prime and boost' vaccination regimens.
Maximizing Field‐Effect Mobility and Solid‐State Luminescence in Organic Semiconductors (2012)

Conductive and emissive: organic transistors made from a simple styrylanthracene derivative have high charge mobility and high luminescence quantum yields. These properties are attributed to the lack of singlet fission, and challenge the idea that the efficient π interactions required for high mobility always lead to quenching of emission. The transistors emit blue electroluminescence and are stable during operation and storage.
Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita mice (2014)

Angiotensin-converting enzyme 2 (ACE2) is located in several tissues and is highly expressed in renal proximal tubules, where it degrades the vasoconstrictor angiotensin II (ANG II) to ANG-(1-7). Accumulating evidence supports protective roles of ACE2 in several disease states, including diabetic nephropathy. A disintegrin and metalloprotease (ADAM) 17 is involved in the shedding of several transmembrane proteins, including ACE2. Our previous studies showed increased renal ACE2, ADAM17 expression, and urinary ACE2 in type 2 diabetic mice (Chodavarapu H, Grobe N, Somineni HK, Salem ES, Madhu M, Elased KM. PLoS One 8: e62833, 2013). The aim of the present study was to determine the effect of insulin on ACE2 shedding and ADAM17 in type 1 diabetic Akita mice. Results demonstrate increased renal ACE2 and ADAM17 expression and increased urinary ACE2 fragments (≈70 kDa) and albumin excretion in diabetic Akita mice. Immunostaining revealed colocalization of ACE2 with ADAM17 in renal tubules. Renal proximal tubular cells treated with ADAM17 inhibitor showed reduced ACE2 shedding into the media, confirming ADAM17-mediated shedding of ACE2. Treatment of Akita mice with insulin implants for 20 wk normalized hyperglycemia and decreased urinary ACE2 and albumin excretion. Insulin also normalized renal ACE2 and ADAM17 but had no effect on tissue inhibitor of metalloproteinase 3 (TIMP3) protein expression. There was a positive linear correlation between urinary ACE2 and albuminuria, blood glucose, plasma creatinine, glucagon, and triglycerides. This is the first report showing an association between hyperglycemia, cardiovascular risk factors, and increased shedding of urinary ACE2 in diabetic Akita mice. Urinary ACE2 could be used as a biomarker for diabetic nephropathy and as an index of intrarenal ACE2 status.
Non‐steroidal anti‐inflammatory drugs (NSAIDs) in Alzheimer's disease: old and new mechanisms of action (2004)

Alzheimer's disease (AD) is characterized by cerebral deposits of beta-amyloid (A beta) peptides and neurofibrillary tangles (NFT) which are surrounded by inflammatory cells. Epidemiological studies have shown that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD and delays the onset of the disease. It has been postulated that some NSAIDs target pathological hallmarks of AD by interacting with several pathways, including the inhibition of cyclooxygenases (COX) and activation of the peroxisome proliferator-activated receptor gamma. A variety of experimental studies indicate that a subset of NSAIDs such as ibuprofen, flurbiprofen, indomethacin and sulindac also possess A beta-lowering properties in both AD transgenic mice and cell cultures of peripheral, glial and neuronal origin. While COX inhibition occurs at low concentrations in vitro (nM-low microm range), the A beta-lowering activity is observed at high concentrations (< or = 50 microm). Nonetheless, studies with flurbiprofen or ibuprofen in AD transgenic mice show that the effects on A beta levels or deposition are attained at plasma levels similar to those achieved in humans at therapeutic dosage. Still, it remains to be assessed whether adequate concentrations are reached in the brain. This is a crucial aspect that will allow defining the dose-window and the length of treatment in future clinical trials. Here, we will discuss how the combination of anti-amyloidogenic and anti-inflammatory activities of certain NSAIDs may produce a profile potentially relevant to their clinical use as disease-modifying agents for the treatment of AD.
Fountain Communication using Concatenated Codes (2012)

This paper extends linear-complexity concatenated coding schemes to fountain communication over the discrete-time memoryless channel. Achievable fountain error exponents for one-level and multi-level concatenated fountain codes are derived. Several important properties of the concatenated coding schemes in multi-user fountain communication scenarios are demonstrated.
Design, Synthesis, and Evaluation of a New Generation of Modular Nucleophilic Glycine Equivalents for the Efficient Synthesis of Sterically Constrained α-Amino Acids (2006)

A new generation of modular achiral glycine equivalents have been evaluated with respect to their synthetic utility for the production of tailor-made, sterically constrained alpha-amino acids, which proved to be the most efficient approach developed to date for the synthesis of symmetrical alpha,alpha-disubstituted-alpha-amino acids. Among the new series of achiral glycine equivalents, one was found to be a superior glycine derivative for the Michael additions with various (R)- or (S)-N-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones representing a general and practical synthesis of sterically constrained beta-substituted pyroglutamic acids. In particular, the application of these complexes allowed for the preparation of several beta-substituted pyroglutamic acids which include electron-releasing and sterically demanding substituents in the structure thus increasing the synthetic efficiency and expanding the generality of these Michael addition reactions.
Cloning of a cDNA Encoding ATP Sulfurylase from Arabidopsis thaliana by Functional Expression in Saccharomyces cerevisiae (1994)

ATP sulfurylase, the first enzyme in the sulfate assimilation pathway of plants, catalyzes the formation of adenosine phosphosulfate from ATP and sulfate. Here we report the cloning of a cDNA encoding ATP sulfurylase (APS1) from Arabidopsis thaliana. APS1 was isolated by its ability to alleviate the methionine requirement of an ATP sulfurylase mutant strain of Saccharomyces cerevisiae (yeast). Expression of APS1 correlated with the presence of ATP sulfurylase enzyme activity in cell extracts. APS1 is a 1748-bp cDNA with an open reading frame predicted to encode a 463-amino acid, 51,372-D protein. The predicted amino acid sequence of APS1 is similar to ATP sulfurylase of S. cerevisiae, with which it is 25% identical. Two lines of evidence indicate that APS1 encodes a chloroplast form of ATP sulfurylase. Its predicted amino-terminal sequence resembles a chloroplast transit peptide; and the APS1 polypeptide, synthesized in vitro, is capable of entering isolated intact chloroplasts. Several genomic DNA fragments that hybridize with the APS1 probe were identified. The APS1 cDNA hybridizes to three species of mRNA in leaves (1.85, 1.60, and 1.20 kb) and to a single species of mRNA in roots (1.85 kb).
Discovery of Superior Enzymes by Directed Molecular Evolution (2001)

Natural selection has created optimal catalysts that exhibit their convincing performance even with a number of sometimes counteracting constraints. Optimal performance of enzyme catalysis does not refer necessarily to maximum reaction rate. Rather, it may involve a compromise between specificity, rate, stability, and other chemical constraints ; in some cases, it may involve aintelligento control of rate and specificity. Because enzymes are capable of catalyzing reactions under mild conditions and with high substrate specificity that often is accompanied by high regioand enantioselectivity, it is not surprising that a continually increasing number of industrial and academic reports concern the use of enzyme catalysts in chemical synthesis as well as in biochemical and biomedical applications. However, the demands of modern synthesis and their commercial application were obviously not targeted during the natural evolution of enzymes. Considering a specific, nonnatural application, any property (or combination of properties) of an enzyme may therefore need to be improved. Of course, scientists desired to mimick nature's powerful concepts for tailoring specific enzymatic properties: Following pioneering experiments for evolving molecules in the test tube, evolutionary engineering of biomolecules was successfully realized with first selections of functional nucleic acids (ribozymes) by using the SELEX (systematic evolution of ligands by exponential enrichment with integrated optimization by non-linear analysis) procedure, 8] and with the development of high-affinity ligands (aptamers) by using similar techniques. Meanwhile, evolutionary engineering, also termed adirected evolutiono, has emerged as a key technology for biomolecular engineering and generated impressive results in the functional adaptation of enzymes to artificial environments. Certainly, evolution in the laboratory does not come to a halt at the optimization of single genes and proteins. Recent results excitingly demonstrate the success of amolecular breedingo of metabolic pathways, and even of complete genomes, and the end is not in sight yet. Directed evolution in the laboratory is highly attractive because its principles are simple and do not require detailed knowledge of structure, function, or mechanism. Essentially like natural evolution, directed evolution comprises the iterative implementation of (1) the generation of a alibraryo of mutated genes, (2) its functional expression, and (3) a sensitive assay to identify individuals showing the desired properties, either by selection or by screening (Figure 1). After each round, the genes of improved variants are deciphered and subsequently serve as parents for another round of optimization. This review covers the most important aspects of directed evolution and summarizes key solutions to problems of optimizing and understanding enzyme function.
Covalent Fullerene Chemistry (1996)

The covalent functionalization of C 60 has developed vigorously over the past 5 years. Several methods are now available for the formation of C 60 monoadducts. Regioselective formation of multiple adducts has allowed study of the changes in chemical and physical properties that occur when the conjugated fullerene chromophore is reduced during an increase in functionalization. The systematic development of covalent fullerene chemistry provides an unprecedented diversity of tailor-made three-dimensional building blocks for technologically interesting materials.
Different Interleukin-1β Converting Enzyme (ICE) Family Protease Requirements for the Apoptotic Death of T Lymphocytes Triggered by Diverse Stimuli (1996)

Two cell permeable peptide fluoromethyl ketone inhibitors of Interleukin-1 beta converting enzyme (ICE) family proteases were tested as inhibitors of apoptotic cell death of T lymphocytes at various stages of differentiation. The CPP-32-like protease activity in apoptotic cell lysates was blocked by both the ICE inhibitor Cbz-Val-Ala-Asp(OMe)-fluoromethyl ketone (ZVAD-FMK) as well as its truncated analog Boc-Asp(OMe)-fluoromethyl ketone (BD-FMK), which failed to block ICE. In vitro apoptotic death in murine thymocytes triggered by the independent agents dexamethasone, etoposide, radiation, anti-Fas, and anti-CD3 was blocked equally well by BD-FMK and ZVAD-FMK, but not by the control reagent Cbz-Phe-Ala-fluoromethyl ketone. In activated T cell blasts, while anti-CD3/ Fas-induced death was almost completely inhibited by both ZVAD-FMK, and BD-FMK, death induced by dexamethasone, etoposide, or irradiation was more sensitive to inhibition by BD-FMK. In the murine T cell line CTLL-2, apoptotic death induced by IL-2 withdrawal, etoposide, or dexamethasone was inhibited by BD-FMK, while ZVAD-FMK was without effect. These data indicate that ICE-family proteases comprise a common functional step in distinct T cell apoptotic death pathways, but suggest that different family members are likely to be critical in various differentiated T cell types, even when triggered by the same stimulus.
Hypoxia and Vascular Endothelial Growth Factor Selectively Up-regulate Angiopoietin-2 in Bovine Microvascular Endothelial Cells (1999)

Recent studies have shown that the angiopoietin-Tie2 system is a predominant regulator of vascular integrity. In this study, we investigated the effect of two known angiogenic stimuli, hypoxia and vascular endothelial growth factor (VEGF), on these molecules. VEGF induced both a time- and concentration-dependent increase in angiopoietin-2 (Ang2) mRNA expression in bovine microvascular endothelial cells. This up-regulation was derived primarily from an increased transcription rate as evidenced by nuclear run-on assay and mRNA decay study. The increased Ang2 expression upon VEGF treatment was almost totally abolished by inhibition of tyrosine kinase or mitogen-activated protein kinase and partially by suppression of protein kinase C. Hypoxia also directly increased Ang2 mRNA expression. In contrast, Ang1 and Tie2 responded to neither of these stimuli. The enhanced Ang2 expression following VEGF stimulation and hypoxia was accompanied by de novo protein synthesis as detected by immunoprecipitation. In a mouse model of ischemia-induced retinal neovascularization, Ang2 mRNA was up-regulated in the ischemic inner retinal layer, and remarkable expression was observed in neovascular vessels. These data suggest that both hypoxia- and VEGF-induced neovascularization might be facilitated by selective induction of Ang2, which deteriorates the integrity of preexisting vasculature.
Optimizing Detection of Kidney Transplant Injury by Assessment of Donor-Derived Cell-Free DNA via Massively Multiplex PCR (2018)

Standard noninvasive methods for detecting renal allograft rejection and injury have poor sensitivity and specificity. Plasma donor-derived cell-free DNA (dd-cfDNA) has been reported to accurately detect allograft rejection and injury in transplant recipients and shown to discriminate rejection from stable organ function in kidney transplant recipients. This study used a novel single nucleotide polymorphism (SNP)-based massively multiplexed PCR (mmPCR) methodology to measure dd-cfDNA in various types of renal transplant recipients for the detection of allograft rejection/injury without prior knowledge of donor genotypes. A total of 300 plasma samples (217 biopsy-matched: 38 with active rejection (AR), 72 borderline rejection (BL), 82 with stable allografts (STA), and 25 with other injury (OI)) were collected from 193 unique renal transplant patients; dd- cfDNA was processed by mmPCR targeting 13,392 SNPs. Median dd-cfDNA was significantly higher in samples with biopsy-proven AR (2.3%) versus BL (0.6%), OI (0.7%), and STA (0.4%) (<i>p</i> < 0.0001 all comparisons). The SNP-based dd-cfDNA assay discriminated active from non-rejection status with an area under the curve (AUC) of 0.87, 88.7% sensitivity (95% CI, 77.7⁻99.8%) and 72.6% specificity (95% CI, 65.4⁻79.8%) at a prespecified cutoff (>1% dd-cfDNA). Of 13 patients with AR findings at a routine protocol biopsy six-months post transplantation, 12 (92%) were detected positive by dd-cfDNA. This SNP-based dd-cfDNA assay detected allograft rejection with superior performance compared with the current standard of care. These data support the feasibility of using this assay to detect disease prior to renal failure and optimize patient management in the case of allograft injury.
Denileukin Diftitox for the Treatment of Panniculitic Lymphoma (2002)

A 24-year-old white woman presented with a 9-month history of proximal extremity nodules, associated with fevers and arthralgias, that had only a partial response to a combination of oral prednisone, topical betamethasone ointment, and topical calcipotriene ointment.