gebhart/patrepeval huggingface dataset:
Validation of cytochrome p450 1b1 as a target for the enzyme prodrug therapy of cancer (2005)

This study is comprised of three parts including: (1) clinical validation of cytochrome P450 CYP1B1 in clinical head and neck squamous cell carcinoma (HNSCC) and associated pre-malignant tissue, (2) the identification of a human tumour xenograft model which exhibits either constitutive or inducible expression of CYP1B1 for the evaluation of novel prodrug therapies in vivo, and (3) the identification of stable prodrugs targeted at CYPl-family enzymes designed to deliver nitric oxide to tumours.\n\nCYP1B1 protein was detected in HNSCC by immunohistochemistry (IHC) with a selective monoclonal antibody and was over-expressed to a high frequency in carcinoma (94 %, n = 70) and associated pre-malignant, hyperplastic (100 %, n = 14), and dysplastic tissues (100 %, n = 22). Quantitative analysis of CYP1B1 staining intensity by spectral imaging microscopy facilitated correlations with other clinico-pathological parameters including tumour grade, stage and anatomical site. CYP1B1 is mainly localised in the cancer tissue and is not present in adjacent stromal tissue, suggesting it may be a possible target for the enzyme prodrug therapy of cancer.\n\nA primary human tumour xenograft model was identified that constitutively expresses CYP1B1. Target enzyme protein expression was also inducible in a time- and dose-dependent manner in vivo as detected by western blotting, IHC and spectral imaging microscopy. Parallel studies also demonstrated CYPlA1 induction in the MCF-7 breast tumour xenograft model. This work has helped validate two potential human tumour xenograft models for the in vivo evaluation of both CYP1A1 - and CYP1B1 -activated prodrugs for cancer therapy.\n\nIn order to exploit the cytotoxic and hypoxic cell radiosensitising properties of nitric oxide (NO•), 10 novel benzo- or pyrido-fused indole oximes designed as prodrugs for NO• were screened for their selectivity for CYPl-family enzymes. GCI 510 was identified as a selective prodrug for CYP1Al, which generated NO• efficiently. This study has contributed to an understanding of the structural features of these prodrugs which confer selectivity for individual CYPl-family enzymes. Future work will seek to identify CYP1B1-selective prodrugs for NO• based on data from this study.
Biodistribution of Radiolabeled, Formulated Gadopentetate, Gadoteridol, Gadoterate, and Gadodiamide in Mice and Rats (1995)

The molecular feature found to be most important in differentiating the four chelates evaluated is the presence or absence of a macrocyclic structure. The Gd chelates containing this structure, gadoteridol and gadoterate, have the lowest residual Gd at long residence times in both mice and rats. The order of residual whole body Gd at 14 days (lowest to highest) was: gadoteridol integral of gadoterate < or = gadopentetate << gadodiamide. The only excipient that affected the biodistribution was found in the gadodiamide formulation where the addition of 5% calcium (DTPA-BMA) reduced residual Gd to just less than 10 times greater than that found for the macrocyclic chelates with the lowest residual Gd, gadoteridol and gadoterate.
Cancer vaccines (2004)

Cancer vaccines - a dream or a reality? There is no doubt that a time will come when this new approach to cancer treatment will provide opportunities that will be both complementary and synergistic with existing treatments. Novelty is often linked to risk, and if there is a given medical field that desperately needs therapeutic improvement, cancer is it. Recent advances on the understanding of the functioning and manipulation of the immune system and on the host-tumour relationship, and on tumour escape, will soon pay off. However, the development of cancer vaccines is not an easy undertaking and the multitude of obstacles are presented and reviewed in this article. The cancer vaccine 'detractors' that are arguing negatively on the chances of success are, to this date, correct. Nevertheless, a parallel could be drawn from the monoclonal antibodies, which have suffered from a long and difficult history, to hold promise in man. Recent technological progress has once again demonstrated that one can eventually bypass the commonly accepted barriers, as there are now monoclonal-based products currently helping patients. The entire oncology community is eagerly awaiting the next chapter in the cancer vaccine story.
Synthesis and Biological Activity of Folic Acid and Methotrexate Analogues Containing <scp>l</scp>-<i>threo</i>-(2<i>S</i>,4<i>S</i>)-4-Fluoroglutamic Acid and <scp>dl</scp>-3,3-Difluoroglutamic Acid (1996)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTSynthesis and Biological Activity of Folic Acid and Methotrexate Analogues Containing l-threo-(2S,4S)-4-Fluoroglutamic Acid and dl-3,3-Difluoroglutamic AcidBarry P. Hart, William H. Haile, Nicholas J. Licato, Wanda E. Bolanowska, John J. McGuire, and James K. CowardCite this: J. Med. Chem. 1996, 39, 20, 4134Publication Date (Web):September 27, 1996Publication History Published online27 September 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm960521qhttps://doi.org/10.1021/jm960521qcorrectionACS PublicationsCopyright © 1996 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views505Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Get e-Alertsclose Get e-Alerts
Safety and Efficacy of Methylene Blue Combined with Artesunate or Amodiaquine for Uncomplicated Falciparum Malaria: A Randomized Controlled Trial from Burkina Faso (2008)

ClinicalTrials.gov NCT00354380.
Direct electron transfer in nanostructured sol–gel electrodes containing bilirubin oxidase (2007)

Bilirubin oxidase encapsulated within a silica sol-gel/carbon nanotube composite electrode effectively catalyzed the reduction of molecular oxygen into water through direct electron transfer at the carbon nanotube electrode surface. In this nanocomposite approach, the silica matrix is designed to be sufficiently porous for substrate molecules to have access to the enzyme and yet provides a protective cage for immobilization without affecting biological activity. The incorporation of carbon nanotubes adds electrical connectivity and increases active electrode surface area. The standard surface electron transfer rate constant was calculated to be 59 s(-1) which indicates that the carbon nanotube side walls are primarily responsible for electron transfer. The use of direct electron transfer processes simplifies biofuel cell fabrication by eliminating the need for redox mediator and ion-conducting separators.
Creation of Controlled Brønsted Acidity on a Zeotypic Mesoporous Chromium(III) Carboxylate by Grafting Water and Alcohol Molecules (2006)

This paper reports a new way of modulating the strength of the Brønsted acid sites of a porous solid. Our approach consists of the grafting of various polar molecules (H2O, CD3OH, CF3CH2OH, and (CF3)2CHOH) on MIL-100(Cr), a mesoporous crystallized chromium carboxylate with accessible unsaturated metal sites. We demonstrate, using infrared spectroscopy, that all these compounds do coordinate on the coordinatively unsaturated Cr3+ sites. This generates controlled Brønsted acid sites whose strength, measured by CO adsorption at 100 K, depends on the nature of the adsorbate. It can vary from H0 = −3 (CD3OH) to −8 ((CF3)2CHOH).
Imidazo[1,2-a]pyridine 1-oxide. Synthesis and chemistry of a novel type of N-oxide (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImidazo[1,2-a]pyridine 1-oxide. Synthesis and chemistry of a novel type of N-oxideElli S. Hand and William W. PaudlerCite this: J. Org. Chem. 1978, 43, 4, 658–663Publication Date (Print):February 1, 1978Publication History Published online1 May 2002Published inissue 1 February 1978https://pubs.acs.org/doi/10.1021/jo00398a030https://doi.org/10.1021/jo00398a030research-articleACS PublicationsRequest reuse permissionsArticle Views788Altmetric-Citations35LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to inhibit blood—brain barrier disruption in multiple sclerosis (2009)

Rolipram, a prototypic phosphodiesterase-4 inhibitor, is highly effective in suppressing Th1 autoimmunity in multiple animal models, including experimental autoimmune encephalomyelitis. In addition, rolipram has been extensively studied as a potential neuroprotective agent. Based on its anti-inflammatory activity, we tested the efficacy of rolipram in suppressing inflammatory disease activity in multiple sclerosis in a proof-of-principle phase I/II open-label clinical trial. Enrolled MS patients were evaluated by monthly MRI and clinical examinations during 3 months (four MRIs) of pretreatment baseline and 8 months of rolipram therapy. The primary outcome was a change in contrast-enhanced lesions between baseline and the last 4 months of rolipram therapy. Previously defined biomarkers of rolipram-mediated immunomodulation were evaluated during the study. The trial was stopped prematurely because the drug was poorly tolerated and because of safety concerns: we observed an increase, rather than decrease, in the brain inflammatory activity measured by contrast-enhanced lesions on brain MRI. At the administered doses rolipram was active in vivo as documented by immunological assays. We conclude that the reasons underlying the discrepancy between the therapeutic efficacy of rolipram in experimental autoimmune encephalomyelitis versus multiple sclerosis are at present not clear.
The chemotherapeutic effects of lapacho tree extract: β-lapachone (2014)

Cancer, a serious problem throughout the world, needs more efficient drugs for clinical applications. One potential chemotherapeutic drug is β-lapachone. The study of β-lapachone begins from 1977. This commentary is going to discuss the current understanding for the therapeutic uses of β-lapachone
An Integrated Approach to Locality-Conscious Processor Allocation and Scheduling of Mixed-Parallel Applications (2008)

Complex parallel applications can often be modeled as directed acyclic graphs of coarse-grained application tasks with dependences. These applications exhibit both task and data parallelism, and combining these two (also called mixed parallelism) has been shown to be an effective model for their execution. In this paper, we present an algorithm to compute the appropriate mix of task and data parallelism required to minimize the parallel completion time (makespan) of these applications. In other words, our algorithm determines the set of tasks that should be run concurrently and the number of processors to be allocated to each task. The processor allocation and scheduling decisions are made in an integrated manner and are based on several factors such as the structure of the task graph, the runtime estimates and scalability characteristics of the tasks, and the intertask data communication volumes. A locality-conscious scheduling strategy is used to improve intertask data reuse. Evaluation through simulations and actual executions of task graphs derived from real applications and synthetic graphs shows that our algorithm consistently generates schedules with a lower makespan as compared to Critical Path Reduction (CPR) and Critical Path and Allocation (CPA), two previously proposed scheduling algorithms. Our algorithm also produces schedules that have a lower makespan than pure task- and data-parallel schedules. For task graphs with known optimal schedules or lower bounds on the makespan, our algorithm generates schedules that are closer to the optima than other scheduling approaches.
Genome characteristics of facultatively symbiotic <i>Frankia</i> sp. strains reflect host range and host plant biogeography (2006)

Soil bacteria that also form mutualistic symbioses in plants encounter two major levels of selection. One occurs during adaptation to and survival in soil, and the other occurs in concert with host plant speciation and adaptation. Actinobacteria from the genus Frankia are facultative symbionts that form N(2)-fixing root nodules on diverse and globally distributed angiosperms in the "actinorhizal" symbioses. Three closely related clades of Frankia sp. strains are recognized; members of each clade infect a subset of plants from among eight angiosperm families. We sequenced the genomes from three strains; their sizes varied from 5.43 Mbp for a narrow host range strain (Frankia sp. strain HFPCcI3) to 7.50 Mbp for a medium host range strain (Frankia alni strain ACN14a) to 9.04 Mbp for a broad host range strain (Frankia sp. strain EAN1pec.) This size divergence is the largest yet reported for such closely related soil bacteria (97.8%-98.9% identity of 16S rRNA genes). The extent of gene deletion, duplication, and acquisition is in concert with the biogeographic history of the symbioses and host plant speciation. Host plant isolation favored genome contraction, whereas host plant diversification favored genome expansion. The results support the idea that major genome expansions as well as reductions can occur in facultative symbiotic soil bacteria as they respond to new environments in the context of their symbioses.
Robustness analysis on a high bandwidth disk drive servo system with an instrumented suspension (1999)

The magnetic disk drive industry is expected to reach track densities of 40,000 tracks per inch by early in the next century. Successful operation at such high track density requires an increase in the closed-loop bandwidth of the head positioning servo-system. Resonance modes in the suspension of hard disk drives limit the closed-loop bandwidth. A high bandwidth disk drive servo system with an instrumented suspension has been proposed by the authors. As an extension of the previous work, this paper presents analysis on stability robustness of the system. It is shown that although the proposed active vibration control scheme is a non-collocated problem, high frequency spillover does not cause instability. Furthermore, closed-loop stability is maintained when the actual frequencies deviate by as much as 40% of the nominal values for compensated flexible modes.
Applications of Deep Reinforcement Learning in Communications and Networking: A Survey (2019)

This paper presents a comprehensive literature review on applications of deep reinforcement learning (DRL) in communications and networking. Modern networks, e.g., Internet of Things (IoT) and unmanned aerial vehicle (UAV) networks, become more decentralized and autonomous. In such networks, network entities need to make decisions locally to maximize the network performance under uncertainty of network environment. Reinforcement learning has been efficiently used to enable the network entities to obtain the optimal policy including, e.g., decisions or actions, given their states when the state and action spaces are small. However, in complex and large-scale networks, the state and action spaces are usually large, and the reinforcement learning may not be able to find the optimal policy in reasonable time. Therefore, DRL, a combination of reinforcement learning with deep learning, has been developed to overcome the shortcomings. In this survey, we first give a tutorial of DRL from fundamental concepts to advanced models. Then, we review DRL approaches proposed to address emerging issues in communications and networking. The issues include dynamic network access, data rate control, wireless caching, data offloading, network security, and connectivity preservation which are all important to next generation networks, such as 5G and beyond. Furthermore, we present applications of DRL for traffic routing, resource sharing, and data collection. Finally, we highlight important challenges, open issues, and future research directions of applying DRL.
A comparison of the toxicity of the coccidiostats diaveridine and pyrimethamine in the chick and the effect of an antibiotic on the anti-folic activity of pyrimethamine. (1966)

SUMMARY Three experiments were carried out to compare the toxicity of the coccidiostats pyrimethamine and diaveridine in the fowl. In 2 of the experiments pyrimethamine and diaveridine were fed at a level of 0·0035% in the diet of hormone-treated female chicks. The results for both experiments showed that the pyrimethamine was toxic at the level given, and resulted in haematological abnormality and a severe inhibition of hormone-stimulated oviduct growth. Addition of zinc bacitracin to the pyrimethamine-containing diet failed to effect any alleviation of the toxic syndrome. The diaveridine had no toxic effects. In the third experiment, pyrimethamine was fed at a level of 0·0035% in the diet, and diaveridine at 0·0035 and 0·007%. As in the first 2 experiments, the pyrimethamine was toxic, but the diaveridine, at both levels, was non-toxic when assessed by the criteria of blood picture and hormone-stimulated oviduct growth. The results obtained are discussed in the light of the relevant literature.
Characteristics of Strontium Aluminate Crystals Used for Long‐Duration Phosphors (1998)

Sr 3 Al 2 O 6 , SrAl 2 O 4 , SrAl 4 O 7 , and SrAl 12 O 19 that have been doped with Eu 2+ and Dy 3+ ions have been grown by a floating‐zone technique for application as long‐duration phosphors. Long‐duration phosphorescence with a variety of colors has been observed in SrA l2 O 4 , SrAl 4 O 7 , and SrAl 12 O 19 crystals that have been doped with Eu 2+ and Dy 3+ ions. The peak wavelength of the phosphorescence is 520 nm for SrAl 2 O 4 , 480 nm for SrAl 4 O 7 , and 400 nm for SrAl 12 O 19 . The phosphorescence is characterized by decay times that have been analyzed by a curve‐fitting technique.
Chemical inactivation of aflatoxins in peanut and cottonseed meals (1970)

Abstract Organic and inorganic reagents have been tested for destruction or inactivation of the aflatoxins present in peanut and cottonseed meals. The treatments were made in a special laboratory‐scale reactor, and were evaluated by determination of the aflatoxins in the products by thin layer chromatography. In some instances, a larger pilot‐plant scale reactor was used. Ammonia, methylamine, sodium hydroxide and formaldehyde reduced aflatoxin levels and appear practical for large scale treatments. Effects of various reaction parameters including time, temperature and moisture content on the efficiency of these reagents are presented.
Nanoflow LC/IMS-MS and LC/IMS-CID/MS of protein mixtures (2004)

A simple ion trap/ion mobility/time-of-flight (TOF) mass spectrometer has been coupled with nanoflow liquid chromatography to examine the feasibility of analyzing mixtures of intact proteins. In this approach proteins are separated using reversed-phase chromatography. As components elute from the column, they are electrosprayed into the gas phase and separated again in a drift tube prior to being dispersed and analyzed in a TOF mass spectrometer. The mobilities of ions through a buffer gas depend upon their collision cross sections and charge states; separation based on these gas-phase parameters provides a new means of simplifying mass spectra and characterizing mixtures. Additionally it is possible to induce dissociation at the exit of the drift tube and examine the fragmentation patterns of specific protein ion charge states and conformations. The approach is demonstrated by examining a simple three-component mixture containing ubiquitin, cytochrome c, and myoglobin and several larger prepared protein mixtures. The potential of this approach for use in proteomic applications is considered.
Effect of pilocarpine hydrochloride on salivary production in previously irradiated head and neck cancer patients. (2006)

Administration of 5-mg pilocarpine hydrochloride tablets three times daily significantly improved salivary production and clinical symptomatology secondary to radiation-induced hyposalivation with minimal side-effects. In addition, this study showed that WST is a fast, technically simple and highly reliable method to study salivary production in prospective studies.
Biocatalytic carboxylation of phenol derivatives: kinetics and thermodynamics of the biological Kolbe–Schmitt synthesis (2015)

Microbial decarboxylases, which catalyse the reversible regioselective ortho-carboxylation of phenolic derivatives in anaerobic detoxification pathways, have been studied for their reverse carboxylation activities on electron-rich aromatic substrates. Ortho-hydroxybenzoic acids are important building blocks in the chemical and pharmaceutical industries and are currently produced via the Kolbe-Schmitt process, which requires elevated pressures and temperatures (≥ 5 bar, ≥ 100 °C) and often shows incomplete regioselectivities. In order to resolve bottlenecks in view of preparative-scale applications, we studied the kinetic parameters for 2,6-dihydroxybenzoic acid decarboxylase from Rhizobium sp. in the carboxylation- and decarboxylation-direction using 1,2-dihydroxybenzene (catechol) as starting material. The catalytic properties (K(m), V(max)) are correlated with the overall thermodynamic equilibrium via the Haldane equation, according to a reversible random bi-uni mechanism. The model was subsequently verified by comparing experimental results with simulations. This study provides insights into the catalytic behaviour of a nonoxidative aromatic decarboxylase and reveals key limitations (e.g. substrate oxidation, CO2 pressure, enzyme deactivation, low turnover frequency) in view of the employment of this system as a 'green' alternative to the Kolbe-Schmitt processes.