gebhart/patrepeval huggingface dataset:
Inhibition of chemokine-induced chemotaxis of monkey leukocytes by mu-opioid receptor agonists. (2000)

It is recognized that chemotaxis and phagocytosis constitute the first line of defense in the immune system, and chemokines function mainly as chemoattractants for phagocytic cells, recruiting monocytes and neutrophils from the blood to sites of infection. In this study, chemotaxis of monkey leukocytes was evaluated using human chemokines IL-8 (interleukin-8), MIP-1 beta and RANTES as the chemoattractants, and the effects of micro-opioid receptor agonists, morphine, DAMGO, methadone and endomorphine, on the efficiency of chemotaxis were examined. It was found that human chemokines served well as chemoattractants for monkey leukocytes, and similar to the human system, chemokine-induced chemotaxis of monkey leukocytes was inhibited in the presence of micro-opioid receptor agonists. The inhibition could be reversed by naloxone, a specific micro-opioid receptor antagonist. These studies further support the value of the monkey model for drug abuse studies in humans, as well as suggest that opioids such as morphine may alter immune functions through micro-opioid receptors on leukocytes.
Recently approved therapies in acute myeloid leukemia: A complex treatment landscape (2018)

Acute myeloid leukemia (AML) is a heterogeneous disease. Until recently, treatment for patients with AML was limited to induction chemotherapy with cytarabine and anthracycline or hypomethylating agents, and, in some instances, allogeneic hematopoietic stem cell transplant. With the recent approval of new therapies-i.e., CPX-351, enasidenib, ivosidenib, gemtuzumab ozogamicin, and midostaurin-a new era in AML treatment has emerged. Comprehensive diagnostic testing, such as cytogenetic and molecular testing, is necessary for establishing patient eligibility for these new agents and should be performed in a timely manner. However, choosing a therapy for patients who are eligible for multiple treatments may be a complex process, particularly for patients with newly diagnosed AML. This review discusses data, including associated safety profiles that supported these recent approvals, and provides insights to help clinicians navigate new therapy options for this devastating disease. Given the heterogeneity of AML, the treatment landscape will likely continue to grow and evolve as additional agents (and their combinations) are approved for the treatment of subpopulations of patients with AML. Physicians will need to remain abreast of the ever-changing treatment landscape.
Activin expression by cultured human retinal pigment epithelial cells. (1994)

These results suggest that activin A can act as an autocrine-paracrine growth regulator in RPE cells and may help control cellular growth in ocular development and proliferative eye disease.
Structure-Based Design of Novel Dihydroalkoxybenzyloxopyrimidine Derivatives as Potent Nonnucleoside Inhibitors of the Human Immunodeficiency Virus Reverse Transcriptase (1998)

Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-on e, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration, <1 nM) but showed no detectable cytotoxicity at concentrations as high as 100 microM.
A Comprehensive Expression Analysis of Cancer Testis Antigens in Head and Neck Squamous Cell Carcinoma Revels MAGEA3/6 as a Marker for Recurrence (2015)

Despite significant advances in the treatment of head and neck squamous cell carcinoma (HNSCC), the survival rate has not changed in the last decades. Therefore, the development of novel therapeutic strategies is pursued. Cancer-testis antigens (CTA) are strong immunogenic proteins with a tumor-restricted expression pattern, and are considered ideal targets for tumor-specific immunotherapeutic approaches. In this study, using an in silico approach, we selected, among 139 previously described CTA, candidates to be evaluated in 89 HNSCC and 20 normal mucosa samples. SPANX-CD (71.9%), MAGEB2 (44.9%), MAGEA1 (44.9%), MAGEB6 (32.6%), and CXORF48 (27.0%) were found frequently expressed in HNSCC, and over 85% of the tumors expressed at least one of these five CTAs. The mRNA positivity of CXORF48, MAGEB6, and CRISP2 presented significant associations with recognized clinical features for poor outcome. Furthermore, MAGEA3/6 positivity was associated with significantly better disease-free survival (DFS, P = 0.014), and the expression of this antigen was shown to be an independent prognostic factor for tumor recurrence. In conclusion, one of five selected CTAs is expressed in at least 85% of the HNSCCs, suggesting a possible usage as target for immunotherapeutic approaches, and the mRNA-positivity for MAGEA3/6 is shown to be an independent marker for DFS.
Synthetic triterpenoids inhibit growth, induce apoptosis and suppress pro-survival Akt, mTOR and NF-{kappa}B signaling proteins in colorectal cancer cells. (2010)

Lack of apoptotic cell death has been implicated in malignant transformation and resistance to anticancer therapies. The promotion of apoptosis in cancer cells could potentially lead to the regression and improved prognosis of refractory colorectal cancer. Synthetic triterpenoids have shown strong antitumorigenic activity towards diverse cancer cell types, but have not been investigated for colorectal cancer. In the present study, we tested the apoptosis-inducing activity of oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) and its C-28 methyl ester (CDDO-Me) and C-28 imidazole (CDDO-Im) derivatives in colorectal cancer cells lines. Cell growth/viability assay (MTS) demonstrated that colorectal cancer cells are highly sensitive to CDDO-Me at concentrations of 1.25 to 10 microM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the cleavage of PARP-1, activation of procaspases -3, -8, and -9 and mitochondrial depolarization. Induction of apoptosis by CDDO-Me was associated with the inhibition of pro-survival Akt, NF-kappaB and mTOR signaling proteins and NF-kappaB-regulated anti-apoptotic Bcl-2, Bcl-xL, Bad and survivin. These studies provide rationale for clinical evaluation of CDDO-Me for the treatment of advanced chemotherapy refractory colorectal cancer.
Protease Inhibitors Potentiate Smooth Muscle Relaxation Induced by Vasoactive Intestinal Peptide in Isolated Human Bronchi (1990)

To examine the role of endogenous proteases in limiting the bronchodilating effects of vasoactive intestinal peptide (VIP) in human airway, we studied precontracted bronchial rings from five nonsmokers undergoing heart-lung transplantation for pulmonary hypertension, either primary or secondary to congenital heart disease. The protease inhibitors aprotinin, leupeptin, phosphoramidon, and soybean trypsin inhibitors significantly potentiated the bronchodilator response to VIP. Even in the presence of the four protease inhibitors, VIP-induced bronchodilation reversed spontaneously in some tissues. These studies show that degradation by endogenous airway proteases is an important determinant of the bronchodilating potency of VIP in isolated human airway.
Indicating User Agent Capabilities in the Session Initiation Protocol (SIP) (2004)

This specification defines mechanisms by which a Session Initiation
Protocol (SIP) user agent can convey its capabilities and
characteristics to other user agents and to the registrar for its
domain. This information is conveyed as parameters of the Contact
header field. [STANDARDS-TRACK]
5′-Hydrogenphosphonates and 5′-Methylphosphonates of Sugar Modified Pyrimidine Nucleosides as Potential Anti-HIV-1 Agents.1 (1992)

Abstract A number of nucleoside 5′-hydrogerphosphonates and nucleoside 5′-methylphosphonates were prepared, to study their ability to inhibit replication of HIV-1. Two compounds, the 5′-hydrogenphosphonate of 3′-azido-3′-deoxythymidine (AZT-HP, IVc) and of 3′-deoxy-3′-fluorothymidine (FLT-HP, IVa), exhibit potent anti-HIV-1 activity with selectivity indices similar to or better than those of their parent nucleosides.
Tert-butyl hydroperoxide (t-BHP) induced apoptosis and necroptosis in endothelial cells: Roles of NOX4 and mitochondrion (2017)

Oxidative stress causes endothelial death while underlying mechanisms remain elusive. Herein, the pro-death effect of tert-butyl hydroperoxide (t-BHP) was investigated with low concentration (50μM) of t-BHP (t-BHP<sub>L</sub>) and high concentration (500μM) of t-BHP (t-BHP<sub>H</sub>). Both t-BHP<sub>L</sub> and t-BHP<sub>H</sub> induced endothelial cell death was determined. T-BHP<sub>L</sub> induced caspase-dependent apoptosis and reactive oxygen species (ROS) generation, which was inhibited by N-acetyl-L-cysteine (NAC). Furthermore, NADPH oxidase inhibitor diphenyleneiodonium (DPI), NOX4 siRNA, and NOX4 inhibitor GKT137831 reduced t-BHP<sub>L</sub>-induced ROS generation while mitochondrial respiratory chain inhibitors rotenone (Rot), 2-thenoyltrifluoroacetone (TTFA), and antimycin A (AA) failed to do so. NOX4 overexpression resulted in increased ROS generation and Akt expression but decreased sensitivity to t-BHP<sub>L</sub>. In contrast, T-BHP<sub>H</sub> induced LDH release, PI uptake, and cell translucent cytoplasm. RIP1 inhibitor necrostatin-1 (Nec-1), MLKL inhibitor necrosulfonamide (NSA) and silencing RIP1, RIP3, and MLKL inhibited t-BHP<sub>H</sub>-induced cell death while pan-caspase inhibitor Z-VAD-FMK showed no effect. T-BHP<sub>H</sub>-induced ROS production was inhibited by TTFA, AA and Rot while DPI showed no effect. T-BHP<sub>H</sub> induced RIP1/RIP3 interaction, which was decreased by Rot, TTFA, and AA. Silence RIP1 and RIP3 but not MLKL inhibited t-BHP<sub>H</sub>-induced mitochondrial membrane potential (MMP) decrease and ROS production. Moreover, P38MAPK inhibitor SB203580 reversed both t-BHP<sub>L</sub> and t-BHP<sub>H</sub>-induced cell death while inhibitors for ERKs and JNKs showed no obvious effect. These data suggested that t-BHP induced both apoptosis and necroptosis in endothelial cells which was mediated by ROS and p38MAPK. ROS derived from NADPH oxidase and mitochondria contributed to t-BHP<sub>L</sub> and t-BHP<sub>H</sub>-induced apoptosis and necroptosis, respectively.
Stiffness-compensated temperature-insensitive micromechanical resonators (2003)

Polysilicon /spl mu/mechanical resonators utilizing a novel temperature-dependent electrical stiffness design technique to compensate for temperature-induced frequency shifts have been demonstrated with greatly reduced temperature coefficients (TC/sub f/'s) on the order of -0.24 ppm//spl deg/C, which is 67 times smaller than exhibited by previous uncompensated resonators. With this new resonator design, the total frequency excursion over a 300 K to 380 K range has been reduced from 1,280 ppm for an uncompensated device to only 18 ppm, which for the first time, is now small enough to erase lingering concerns regarding the temperature stability of MEMS-based resonators for use in communication applications.
Polymerization of Styrene with Initiator Ionically Bound to High Surface Area Mica: Grafting via an Unexpected Mechanism (1994)

To obtain polystyrene grafted to mica, a free-radical initiator 2,2'-azobis(isobutyramidine hydrochloride) (AIBA) was attached by ion exchange to the surface of an ultrahigh specific surface area (ca. 100 m&lt;sup&gt;2&lt;/sup&gt;/g) muscovite mica powder, and the resulting material was used as an initiator to polymerize styrene. Grafted polymer was indeed obtained, in amounts up to ca. 10 % by weight (ca. 30 % by volume) of polymer based on mica, but it was found that grafting proceeded by an unexpected mechanism. Instead of propagation of free radicals from the surface into the bulk monomer (growth from the surface), grafting took place via attack of growing chains thermally-initiated in the monomer on disproportionation products of AIBA attached to the surface (growth to the surface). The grafted polymer consisted primarily of high molecular weight chains (&lt;i&gt;M&lt;/i&gt; ca. 10&lt;sup&gt;6&lt;/sup&gt;) bound by their headgroups to a very small fraction (less than 1 per 4000) of the surface ion-exchange sites. Consistent with this mechanism, grafted polymer could also be obtained with ''thermally-deactivated' AIBA-mica at rates comparable to those obtained with ''fresh'' AIBA-mica. Grafting was accelerated when 2,2'-azobis(isobutyronitrile) was added to the monomer as an additional initiator.
POLYKETIDE SYNTHASE GENE MANIPULATION: A Structure-Function Approach in Engineering Novel Antibiotics (1995)

Polyketides are produced primarily in microorganisms through a specialized metabolism that is a variation of fatty acid biosynthesis. A strong sequence and mechanistic similarity among many of the fatty acid and polyketide synthase enzymes has led to two paradigms for explaining polyketide biochemistry. In one, polyketides are formed by enzyme complexes consisting of four to seven monofunctional proteins in which the beta-carbonyl groups of the intermediates resulting from the condensation of acetate residues are largely not reduced and cyclization of the intermediates typically produces aromatic compounds. The intermediates in the other model are formed by multifunctional enzymes in which each of the initial condensation products is processed through reduction; reduction and dehydration; or reduction, dehydration, and further reduction cycles to produce highly reduced compounds from acetate, propionate, and butyrate residues. Expression of the genes encoding each type of polyketide synthase, or their mutant forms, has provided much information about the underlying biochemistry and, in some cases, resulted in the formation of novel natural products.
Verifying distributed erasure-coded data (2007)

Erasure coding can reduce the space and band width overheads of redundancy in fault-tolerant data storage and delivery systems. But it introduces the fundamental difficulty of ensuring that all erasure-coded fragments correspond to the same block of data. Without such assurance, a different block may be reconstructed from different subsets of fragments. This paper develops a technique for providing this assurance without the bandwidth and computational overheads associated with current approaches. The core idea is to distribute with each fragment what we call homomorphic fingerprints. These fingerprints preserve the structure of the erasure code and allow each fragment to be independently verified as corresponding to a specific block. We demonstrate homomorphic fingerprinting functions that are secure, efficient, and compact.
Propionyl-Coenzyme A Synthase from Chloroflexus aurantiacus, a Key Enzyme of the 3-Hydroxypropionate Cycle for Autotrophic CO2 Fixation (2002)

The 3-hydroxypropionate cycle has been proposed as a new autotrophic CO(2) fixation pathway for the phototrophic green non-sulfur eubacterium Chloroflexus aurantiacus and for some chemotrophic archaebacteria. The cycle requires the reductive conversion of the characteristic intermediate 3-hydroxypropionate to propionyl-CoA. The specific activity of the 3-hydroxypropionate-, CoA-, K(+)-, and MgATP-dependent oxidation of NADPH in autotrophically grown cells was 0.09 micromol min(-1) mg(-1) protein, which was 2-fold down-regulated in heterotrophically grown cells. Unexpectedly, a single enzyme catalyzes the entire reaction sequence: 3-hydroxypropionate + MgATP + CoA + NADPH + H(+) --> propionyl-CoA + MgAMP + PP(i) + NADP(+) + H(2)O. The enzyme was purified 30-fold to near homogeneity and has a very large native molecular mass between 500 and 800 kDa, with subunits of about 185 kDa as judged by SDS-PAGE, suggesting a homotrimeric or homotetrameric structure. Upon incubation of this new enzyme, termed propionyl-CoA synthase, with the proteinase trypsin, the NADPH oxidation function of the enzyme was lost, whereas the enzyme still activated 3-hydroxypropionate to its CoA-thioester and dehydrated it to acrylyl-CoA. SDS-PAGE revealed that the subunits of propionyl-CoA synthase had been cleaved once and the N-terminal amino acid sequences of the two trypsin digestion products were determined. Two parts of the gene encoding propionyl-CoA synthase (pcs) were identified on two contigs of an incomplete genome data base of C. aurantiacus, and the sequence of the pcs gene was completed. Propionyl-CoA synthase is a natural fusion protein of 201 kDa consisting of a CoA ligase, an enoyl-CoA hydratase, and an enoyl-CoA reductase, the reductase domain containing the trypsin cleavage site. Similar polyfunctional large enzymes are common in secondary metabolism (e.g. polyketide synthases) but rare in primary metabolism (e.g. eukaryotic type I fatty acid synthase). These results lend strong support to the operation of the proposed pathway in autotrophic CO(2) fixation.
Virtual Instrumentation System With Real-Time Visual Feedback and Needle Position Warning Suitable for Ophthalmic Anesthesia Training (2018)

In this paper, the design and development of a novel mannequin-based ophthalmic anesthetic training system with two cameras integrated into it to provide a real-time visual feedback to the trainee is presented. The system developed uses anatomically accurate 3-D printed ocular structures and a novel feature for ophthalmic training system where the trainee is able to see the needle and ocular structures on a monitor in real time during the training. Other new features of the system include a virtual instrument, which has been developed to acquire the images, process, and automatically capture the required information from the images from the cameras. The system is developed in such a way that when a trainee practices using the proposed system, it detects and tracks the needle tip position automatically using an appropriate algorithm. Then, the position of the needle is used to trace the path of the needle, and the system warns if the needle enters locations within the orbital cavity that are classified as unsafe. The entire training session as observed by the two wisely positioned cameras can be recorded; the same can be reviewed by an expert anesthetist at any point of time to give the feedback. The trainee with information provided by the training system and the feedback provided by the expert instructor helps him/her to improve and perform safer regional ophthalmic blocks. The system developed was tested at a pilot study, which comprised of 21 trainees and 20 consultant ophthalmic anesthetists to validate its utility.
IMMUNOTOXINS FOR EX VIVO MARROW PURGING IN AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR ACUTE NONLYMPHOCYTIC LEUKEMIA (1988)

Two potent antimyeloid immunotoxins (IT) were generated by conjugating AML-2-23 (anti-CD14) and MCS-2 (anti-CD13) monoclonal antibodies (mAb) to the ribosome-inactivating phytotoxin, ricin. Both IT selectively bound to target cells, inhibited protein synthesis, and prevented the clonogenic growth of fresh marrow blasts from acute nonlymphocytic leukemia patients as well as KG-1 (ANLL) cells. Cryopreservation did not inhibit IT activity. We conclude that AML-2-23-ricin and MCS-2-ricin show potential for effective ex vivo marrow purging in autologous bone marrow transplantation (ABMT) for ANLL. To our knowledge, this study represents the first evidence of the clinical potential of IT in high-risk ANLL.
Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning (2003)

Ischemic preconditioning (Pre-con) is an adaptive response triggered by a brief ischemia applied before a prolonged coronary occlusion. We tested the hypothesis that repetitive ischemia applied during early reperfusion, i.e., postconditioning (Post-con), is cardio-protective by attenuating reperfusion injury. In anesthetized open-chest dogs, the left anterior descending artery (LAD) was occluded for 60 min and reperfused for 3 h. In controls (n = 10), there was no intervention. In Pre-con (n = 9), the LAD was occluded for 5 min and reperfused for 10 min before the prolonged occlusion. In Post-con (n = 10), at the start of reperfusion, three cycles of 30-s reperfusion and 30-s LAD reocclusion preceded the 3 h of reperfusion. Infarct size was significantly less in the Pre-con (15 +/- 2%, P < 0.05) and Post-con (14 +/- 2%, P < 0.05) groups compared with controls (25 +/- 3%). Tissue edema (% water content) in the area at risk was comparably reduced in Pre-con (78.3 +/- 1.2, P < 0.05) and Post-con (79.7 +/- 0.6, P < 0.05) versus controls (81.5 +/- 0.4). Polymorphonuclear neutrophil (PMN) accumulation (myeloperoxidase activity, Deltaabsorbance.min-1.g tissue-1) in the area at risk myocardium was comparably reduced in Post-con (10.8 +/- 5.5, P < 0.05) and Pre-con (13.4 +/- 3.4, P < 0.05) versus controls (47.4 +/- 15.3). Basal endothelial function measured by PMN adherence to postischemic LAD endothelium (PMNs/mm2) was comparably attenuated by Post-con and Pre-con (15 +/- 0.6 and 12 +/- 0.6, P < 0.05) versus controls (37 +/- 1.5), consistent with reduced expression of P-selectin on coronary vascular endothelium in Post-con and Pre-con. Endothelial function assessed by the maximal vasodilator response of postischemic LAD to acetylcholine was significantly greater in Post-con (104 +/- 6%, P < 0.05) and Pre-con (109 +/- 5%, P < 0.05) versus controls (71 +/- 8%). Plasma malondialdehyde (microM/ml), a product of lipid peroxidation, was significantly less at 1 h of reperfusion in Post-con (2.2 +/- 0.2, P < 0.05) versus controls (3.2 +/- 0.3) associated with a decrease in superoxide levels revealed by dihydroethidium staining in the myocardial area at risk. These data suggest that Post-con is as effective as Pre-con in reducing infarct size and preserving endothelial function. Post-con may be clinically applicable in coronary interventions, coronary artery bypass surgery, organ transplantation, and peripheral revascularization where reperfusion injury is expressed.