gebhart/patrepeval huggingface dataset:
Restriction of Foamy Viruses by APOBEC Cytidine Deaminases (2005)

Foamy viruses (FVs) are nonpathogenic retroviruses infecting many species of mammals, notably primates, cattle, and cats. We have examined whether members of the apolipoprotein B-editing catalytic polypeptide-like subunit (APOBEC) family of antiviral cytidine deaminases restrict replication of simian FV. We show that human APOBEC3G is a potent inhibitor of FV infectivity in cell culture experiments. This antiviral activity is associated with cytidine editing of the viral genome. Both molecular FV clones and primary uncloned viruses were susceptible to APOBEC3G, and viral infectivity was also inhibited by murine and simian APOBEC3G homologues, as well as by human APOBEC3F. Wild-type and bet-deleted viruses were similarly sensitive to this antiviral activity, suggesting that Bet does not significantly counteract APOBEC proteins. Moreover, we did not detect FV sequences that may have been targeted by APOBEC in naturally infected macaques, but we observed a few G-to-A substitutions in humans that have been accidentally contaminated by simian FV. In infected hosts, the persistence strategy employed by FV might be based on low levels of replication, as well as avoidance of cells expressing large amounts of active cytidine deaminases.
Novel Ubiquitin Specific Protease-13 Inhibitors Alleviate Neurodegenerative Pathology (2021)

Ubiquitin Specific Protease-13 (USP13) promotes protein de-ubiquitination and is poorly understood in neurodegeneration. USP13 is upregulated in Alzheimer's disease (AD) and Parkinson's disease (PD), and USP13 knockdown via shRNA reduces neurotoxic proteins and increases proteasome activity in models of neurodegeneration. We synthesized novel analogues of spautin-1 which is a non-specific USP13 inhibitor but unable to penetrate the brain. Our synthesized small molecule compounds are able to enter the brain, more potently inhibit USP13, and significantly reduce alpha-synuclein levels in vivo and in vitro. USP13 inhibition in transgenic mutant alpha-synuclein (A53T) mice increased the ubiquitination of alpha-synuclein and reduced its protein levels. The data suggest that novel USP13 inhibitors improve neurodegenerative pathology via antagonism of de-ubiquitination, thus alleviating neurotoxic protein burden in neurodegenerative diseases.
Multi-junction polymer solar cells: Status and challenges (Conference Presentation) (2018)

Multi-junction device architectures represent a promising strategy to further advance the efficiency of organic solar cells. For solution-processed organic solar cells, tandem and triple junction cells have been reported in the past. Yet, several challenges remain, both in developing new photoactive materials as well crating new recombination layers that serve to interconnect the subcells. We developed new versatile charge recombination layers for solution-processed multi-junction solar cells in n-i-p and p-i-n architectures. The new recombination layers provide an essentially lossless contact in each case, without the need of adjusting the formulations or deposition conditions for six different tandem cells and three different triple-junction solar cells, employing a range of different photoactive layers. The approach permitted realizing complex devices in good yields, providing a power conversion efficiency up to 10%. We will also present a first example of a quadruple-junction polymer solar cell, featuring four different and complementary band gap absorber layers that absorb light up to 1150 nm. The quadruple junction cell is reaches a power conversion efficiency of about 7.5% with an open-circuit voltage of 2.46 V. Measuring the external quantum efficiency (EQE) of the quadruple cells has been accomplished using a protocol using bias light of different wavelengths, involving optical modeling and correcting for the build-up electric field. At present, the efficiency of the quadruple-junction polymer cell is mainly limited by bimolecular recombination in the active layers.
Priming with DNA Enhances Considerably the Immunogenicity of hCG β‐LTB Vaccine (2015)

Immunization with the DNA form of the recombinant hCGβ-LTB vaccine twice at fortnightly interval followed by the proteinic form of the vaccine induces distinctly higher antibody response.
Live biotherapeutic throat spray for respiratory virus inhibition and interferon pathway induction (2022)

Abstract Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory tract (URT), where the resident respiratory microbiome has an important gatekeeper function. In contrast to gut-targeting administration of beneficial bacteria against respiratory viral disease, topical URT administration of probiotics is currently underexplored, especially for the prevention and/or treatment of viral infections. Here, we report the selection and formulation of a broad-acting throat spray with live lactobacilli which induce interferon regulatory pathways and are able to inhibit respiratory viruses. Rational selection of Lactobacillaceae strains was based on safety, applicability, and potential antiviral and immunostimulatory efficacy in the URT. Three strains, Lacticaseibacillus casei AMBR2, Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum WCFS1 significantly reduced the cytopathogenic effects of RSV, influenza A/H1N1 and B viruses, and HCoV-229E coronavirus in co-culture models with bacteria, virus and host cells. Subsequently, these strains were formulated in a throat spray and human monocytes were employed to confirm the formulation process did not reduce the interferon regulatory pathway-inducing capacity. Administration of the throat spray in healthy volunteers revealed that the lactobacilli were capable of temporary colonization of the throat in a metabolically active form.
ChemInform Abstract: Conformational Analysis of a Highly Potent, Constrained Gonadotropin‐ Releasing Hormone Antagonist. Part 2. Molecular Dynamics Simulations. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A New Method for the Preparative Isolation of Chlorogenic Acid Lactones from Coffee and Model Roasts of 5-Caffeoylquinic Acid (2013)

Chlorogenic acid lactones (CQL) are known to contribute to the bitter taste of roasted coffee. CQL might also have beneficial biological activities. Until now, there is a lack of pure standard compounds for quantification and biological testing. Using high-speed countercurrent chromatography, milligram amounts of lactones could be isolated. The structures of 3-O-caffeoyl-γ-quinide, 4-O-caffeoyl-muco-γ-quinide, and 5-O-caffeoyl-epi-δ-quinide were confirmed by 1D and 2D NMR spectroscopy including (13)C NMR data, which were previously not available from the literature. An UHPLC method was developed that enabled the separation of the lactones from roasted coffee in significantly shorter time than conventional HPLC.
CRISPR/Cas9-Mediated Phage Resistance Is Not Impeded by the DNA Modifications of Phage T4 (2014)

Bacteria rely on two known DNA-level defenses against their bacteriophage predators: restriction-modification and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) systems. Certain phages have evolved countermeasures that are known to block endonucleases. For example, phage T4 not only adds hydroxymethyl groups to all of its cytosines, but also glucosylates them, a strategy that defeats almost all restriction enzymes. We sought to determine whether these DNA modifications can similarly impede CRISPR-based defenses. In a bioinformatics search, we found naturally occurring CRISPR spacers that potentially target phages known to modify their DNA. Experimentally, we show that the Cas9 nuclease from the Type II CRISPR system of Streptococcus pyogenes can overcome a variety of DNA modifications in Escherichia coli. The levels of Cas9-mediated phage resistance to bacteriophage T4 and the mutant phage T4 gt, which contains hydroxymethylated but not glucosylated cytosines, were comparable to phages with unmodified cytosines, T7 and the T4-like phage RB49. Our results demonstrate that Cas9 is not impeded by N6-methyladenine, 5-methylcytosine, 5-hydroxymethylated cytosine, or glucosylated 5-hydroxymethylated cytosine.
Conversion of ortho-positronium in low-density oxygen gas (1990)

Conservation of ortho-positronium in oxygen has been investigated by the high-resolution 2 gamma angular correlation method. The oxygen pressure was low enough to suppress possible conversion of para-positronium to ortho-positronium. Silica aerogel was used to form a sufficient number of positronium atoms in a restricted region necessary for the high-resolution angular correlation measurements. The existence of an inelastic conversion process has been reconfirmed. The cross sections for the elastic and inelastic conversion processes have been estimated to be (1.0+or-0.3)*10-19 cm2 and some 10-17 cm2, respectively.
Junctionless ferroelectric field effect transistors based on ultrathin silicon nanomembranes (2014)

The paper reported the fabrication and operation of nonvolatile ferroelectric field effect transistors (FeFETs) with a top gate and top contact structure. Ultrathin Si nanomembranes without source and drain doping were used as the semiconducting layers whose electrical performance was modulated by the polarization of the ferroelectric poly(vinylidene fluoride trifluoroethylene) [P(VDF-TrFE)] thin layer. FeFET devices exhibit both typical output property and obvious bistable operation. The hysteretic transfer characteristic was attributed to the electrical polarization of the ferroelectric layer which could be switched by a high enough gate voltage. FeFET devices demonstrated good memory performance and were expected to be used in both low power integrated circuit and flexible electronics.
Nonbulk Complex Structures in Thin Films of Symmetric Block Copolymers on Chemically Nanopatterned Surfaces (2012)

Thin films of symmetric polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) with a bulk lamellar period of Lo were equilibrated on chemically nanopatterned surfaces that had alternating PS and PMMA preferential wetting stripes. The chemical patterns had a period of LS, and the width of the PMMA wetting stripes was W. We identified a set of four morphologies, two of which are fully three-dimensional. On chemical patterns with LS = 2Lo, as W/L0 increased from 0 to 1, block copolymers formed morphologies including bulk-like structures, nominally, parallel lamellae and vertical lamellae, and two bulk-deviate complex morphologies. On chemical patterns with W/L0 = 0.5, as the commensurability factor, δ = LS/L0, increased from 0.87 to 3.05, block copolymers formed complex three-dimensional structures. At the substrate, the block copolymer had a wetting layer reflecting the chemical pattern. At the free surface, the block copolymer formed lamellar-like structures with period L0 along the direction of the underlying chemically patterned stripes when δ was close to an integer, and fingerprint-like structures when δ was not close to an integer. Morphologies obtained by numerical simulations of a coarse grained model of block copolymers compare favorably with our experimental results and help explain the origin of the observed behavior.
Prospects for Anti-Neoplastic Therapies Based on Telomere Biology (2002)

The maintenance of specialized nucleoprotein structures at the ends of human chromosomes called telomeres is essential for chromosome stability, and plays a fundamental role in the regulation of cellular lifespan. Without new synthesis of telomeres, chromosome ends shorten with progressive cell division, eventually triggering either replicative senescence or apoptosis when telomere length becomes critically short. The regulation of telomerase activity in human cells plays a significant role in the development of cancer. Telomerase is tightly repressed in the vast majority of normal human somatic cells but becomes activated during cell immortalization and in cancers. Recent work has demonstrated that inhibiting or targeting telomerase shows promise as a novel anti-neoplastic strategy; however, the biology of telomeres and telomerase predict that such approaches will differ in important ways from traditional cytotoxic drug therapies. Understanding telomerase biology may eventually lead to several types of clinically effective, telomerase-based therapies for neoplastic disease.
Pharmacological Characterization and Structure Activity Relationship of FXI Antisense Oligonucleotides in Cynomolgus Monkeys. (2009)

Abstract Abstract 2101 Poster Board II-78 The absence of abnormal bleeding associated with congenital deficiencies of the intrinsic coagulation pathway factor, FXI, suggests that this pathway is not important for normal blood coagulation in vivo. However, recent work in mice and higher species demonstrates that the intrinsic pathway is an important contributor to pathologic intravascular thrombosis, suggesting that targeting this pathway may yield effective antithrombotic agents with high safety. We have previously demonstrated that second generation antisense oligonucleotides (ASOs) targeting the intrinsic pathway member FXI were potent antithrombotic agents and that this activity was achieved in several mouse models of thrombosis without any increase in bleeding risk (Zhang et al. ASH 2008). Here we characterize the pharmacological activity, chemical SAR and safety profile of FXI antisense oligonucleotides administered subcutaneously in Cynomologus monkeys. Our first monkey study was designed to address the PK/PD kinetics of FXI ASOs from a single chemical series (20 mers, 5-10-5 MOE Gapmers). Two dose escalation regimes were evaluated (1) 5mg/kg (3wks), 10mg/kg (3 wks) followed by 25 mg/kg (6wks) and (2) 5mg/kg (3wks) followed by 10mg/kg (9 wks). The subsequent study was designed to evaluate chemical SAR around the active ASOs identified in the study 1. FXI antisense oligonucleotides FXI-AS1, FXI-AS2 demonstrated dose and time dependent pharmacologic activity, including, decreased FXI mRNA in liver (up to 90%), decreased FXI protein levels and FXI activity measured in plasma, with a maximal inhibition of &gt;80% observed at 25mg/kg on both schedules, prolonged activated partial thromboplastin times (aPTT), maximal aPTT ratio of 2.O, but no change in prothrombin time (PT) as expected. Similar to previous studies in mouse the anticoagulant activity observed from FXI depletion in monkeys was not associated with increased bleeding risk as assessed in a skin bleeding time test. Additionally, FXI ASOs had no deleterious effects on organ weights, platelets, or on measures of liver and kidney function. The second study confirmed the effects of FXI-AS1 and FXI-AS2 and demonstrated that shorter ASOs with decreased gap size were equally potent. These results further support the development of FXI ASOs as human therapeutics for the treatment of coagulation related disorders with the potential for improved safety profiles. Disclosures: MacLeod: Isis Pharmaceuticals: Employment. Crosby:Isis Pharmaceuticals, Inc.: Employment. Zhao:Isis Pharmaceuticals, Inc.: Employment. Gao:Isis Pharmaceuticals, Inc.: Employment. May:Isis Pharmaceuticals, Inc.: Employment. Zhang:Isis Pharmaceuticals, Inc.: Consultancy. Lowenberg:Isis Pharmaceuticals, Inc.: Consultancy. Levi:Isis Pharmaceuticals, Inc.: Consultancy. Monia:Isis Pharmaceuticals, Inc.: Employment.
Metabolic labelling of -specific glycoproteins in membranes of parasitized rhesus monkey erythrocytes (1980)

Rhesus monkey erythrocytes infected with P. knowlesi at high degrees of synchrony were metabolically labeled in vitro during the early schizont stage, using 14C-amino acids and 14C-glucosamine as precursors. Parasite-specific proteins in purified schizonts and host-cell membranes were characterized by their isoelectric points and molecular masses, using isoelectric focusing in polyacrylamide and dodecyl sulfate polyacrylamide gel electrophoresis, respectively. Both 14C-amino acids and 14C-glucosamine caused labelling of 60,000-90,000D proteins/glycoproteins, focusing between pH 4.5 and pH 5.2. The plasmodial parasites synthesized gangliosides and/or other glycolipids, leading to their appearance in the host cell membrane.
Photodynamic Diagnosis with Oral 5-Aminolevulinic Acid for Upper Urinary Tract Carcinoma: A Prospective Clinical Trial (2020)

<b><i>Background and Purpose:</i></b> In this study, we evaluated the effectiveness and safety of photodynamic diagnosis (PDD) of upper urinary tract carcinoma (UTUC) using oral 5-aminolevulinic acid (5-ALA). <b><i>Materials and Methods:</i></b> Consecutive adult patients with suspected UTUC based on imaging and urine cytology findings were prospectively enrolled from May 2018 to January 2019. 5-ALA (20 mg/kg) was orally administered 2 to 3 hours before diagnostic ureteroscopy (URS). Sixty-three biopsy samples were collected from 20 eligible patients using white light (WL) and PDD-URS. The primary endpoint was sensitivity, and the secondary endpoints were specificity, positive predictive value (PPV) and negative predictive value (NPV), diagnostic accuracy, and safety. <b><i>Results:</i></b> The sensitivity of photodynamic URS was significantly higher than that of WL-URS (93.8% <i>vs</i> 62.5%, <i>p</i> = 0.0025). Although the specificity and PPV were not different between the two procedures, PDD-URS showed a significantly higher NPV (92.3% <i>vs</i> 69.2%, <i>p</i> = 0.027) and accuracy (0.86 <i>vs</i> 0.75, <i>p</i> = 0.0297) than WL-URS. With respect to safety, no grade ≥3 adverse events related to 5-ALA administration occurred in any patients. <b><i>Conclusion:</i></b> We found that PDD-URS with oral 5-ALA is a safe and superior diagnostic tool for detection of UTUC compared with conventional WL-URS.
A randomized phase II study of pemetrexed (P) versus pemetrexed-carboplatin (PC) as second line treatment for patients (pts) with advanced non-small-cell lung cancer (NSCLC)- NVALT 7 (2008)

8050 Background: The role of platinum compounds as part of second line therapies in advanced NSCLC is ill defined. We performed a randomized phase II trial comparing P and PC in pts relapsing after platinum-based chemotherapy. Methods: Main eligibility criteria: histological or cytological proof of advanced NSCLC, relapse > 3 months (mo) after (first-line) platinum-based chemotherapy, normal organ reserve, ECOG PS 0–2, age >18 years and signed informed consent. After stratification, pts were randomized to (A) P 500 mg/m2 i.v. q 3 wks or (B) C AUC 5 and P 500 mg/m2 both iv q 3 wks. Response was assessed 6 weekly according to RECIST and toxicity 3 weekly according to NCI-CTC criteria. The primary endpoint was time to progression (TTP). Secondary endpoints: objective response rate (ORR), overall survival (OS), toxicity. The study was designed to detect a 33% decrease in hazard of progression in the combination arm with 80% power (at α=0.05 two-sided log-rank test). Results: From October 2005 to May 2007 151 males and 89 females, median (range) age 59 (36–84), ECOG PS 0/1/2 33%/58%/9% were enrolled. With data 90% complete and after a median follow up of 10.6 mo, median TTP for arm A was 5.7 mo and for arm B 6.9 mo (HR = 0.8 [0.60, 1.07], p=0.12). ORR: 4% in arm A and 9% in arm B. Median OS: 7.3 mo versus 8.1 mo. Toxicities grade 3/4 was 29% in arm A and 44% in Arm B, mainly hematological without clinical sequel. No patient discontinued treatment due to toxicity. One fatal toxicity was encountered in arm A, none in arm B. Conclusions: PC as second line treatment for relapsed NSCLC resulted in a non significant 20% reduction of hazard of progression as compared to P alone. Based on the statistical assumptions of the study, further testing of CP in phase III setting is not warranted. The role of platinum combinations in relapsed NSCLC seems limited. No significant financial relationships to disclose.
On load balancing in multicomputer/distributed systems equipped with circuit or cut-through switching capability (2000)

For multicomputer or distributed systems that use circuit switching, wormhole routing, or virtual cut-through (the last two are collectively called the cut-through switching), the communication overhead and the message delivery time depend largely upon link contention rather than upon the distance between the source and the destination. That is, a larger communication overhead or a longer delivery delay occurs to a message when it traverses a route with heavier traffic than the one with a longer distance and lesser traffic. This characteristic greatly affects the selection of routes for interprocessor communication and/or load balancing. We consider the load-balancing problem in these types of systems. Our objective is to find the maximum load imbalance that can be eliminated without violating the (traffic) capacity constraint and the route to eliminate the imbalance while keeping the maximum link traffic as low as possible. We investigate the load-balancing problem under various conditions. First, we consider the case in which the excess load on each overloaded node is divisible. We devise a network flow algorithm to solve this type of load balancing problem optimally in polynomial time. Next, we impose the realistic assumption that the system uses a specific routing scheme so that the excess load transferred from an overloaded node to an underloaded node must use the route found by the routing scheme. For this case, we use a graph transformation technique to transform the system graph to another graph to which the same network flow algorithm can be applied to solve the load balancing problem optimally. Finally, we consider the case in which the excess load on each overloaded node is indivisible, i.e., the excess load must be transferred as an entity. We show that the load-balancing problem of this type becomes NP-complete and propose a heuristic algorithm as a solution.
Coordinative chain transfer copolymerization of ethylene and styrene using an ansa-bis(fluorenyl) neodymium complex and dialkylmagnesium (2018)

Coordinative chain transfer copolymerization of ethylene and styrene was successfully achieved using an <italic>ansa</italic>-bisfluorenyl neodymium complex, dialkylmagnesium as a chain transfer agent and di-<italic>n</italic>-butylether as a co-solvent.