gebhart/patrepeval huggingface dataset:
OB-24, a novel selective and potent HO-1 inhibitor, induces a wide spectrum anti-tumor activity in vitro and in vivo and synergizes with chemotherapy drugs (2007)

C82 Mortality from cancer is attributed primarily to the dissemination of primary tumor cells to distant organs, where only limited therapeutic options are available for patients. The new shift toward targeted therapies for metastatic & drug resistant cancer have provided encouraging clinical results and reinforced the effectiveness of targeting cancer-associated targets. Here, we report the anti-tumor and anti-metastatic activity of a novel class of targeted agents that interfere with heme oxygenase 1 (HO-1). HO-1 is a highly-inducible 32 kDa member of the stress protein superfamily that catalyzes the oxidative degradation of heme to biliverdin. We have identified HO-1 to be implicated in the regulation of growth and survival of a large panel of human cancer cell lines. Furthermore, HO-1 was found to be differentially expressed in human cancer tissues, including prostate carcinoma at different stages of progression. OB-24, a novel substituted imidazole, was found to have highly selective inhibitory activity toward HO-1 but not HO-2 enzymatic activity, based on the IC50 inhibitory values for HO-1 (rat spleen) and HO-2 (rat brain), enzymes, respectively. OB-24 was well tolerated by mice at multiple doses up to 100 mg/kg dose when given by intraperitonal as well as intravenous routes. Antitumor activity was seen in the PC-3 prostate carcinoma model, SKMEL-24 melanoma model, HCT-116 colorectal carcinoma model and OVCAR-3 ovarian carcinoma model. The activity of OB-24 in these models was equal to or higher than that of the standard chemotherapy agents: 5-FU, Taxol, Dacarbazine, and Cisplatin. In the PC-3 model, OB-24 showed a dramatic activity (approximately 90% inhibition compared to vehicle alone) when combined with Taxol. Immunohistochemistry studies clearly indicate that the activity of OB-24 combined with taxol significantly inhibited lung metastasis formation. Furthermore, CD-31 staining revealed that OB-24-treated tumors exhibited a significant reduction in vascularization. Similar results on alternative preclinical models will be presented. In summary, our data support the clinical therapeutic utility of selective HO-1 inhibitors for the treatment of advanced and chemotherapy refractory cancers.
Modulation of Renal Apical Organic Anion Transporter 4 Function by Two PDZ Domain–Containing Proteins (2005)

Human organic anion transporter 4 (OAT4) is an apical organic anion/dicarboxylate exchanger in the renal proximal tubules and mediates high-affinity transport of steroid sulfates such as estrone-3-sulfate (E1S) and dehydroepiandrosterone sulfate. Here, two multivalent PDZ (PSD-95/Discs Large/ZO-1) proteins PDZK1 and NHERF1 were examined as interactors of OAT4 by a yeast two-hybrid assay. These interactions require the extreme C-terminal region of OAT4 and the first and fourth PDZ domains of PDZK1 and the first PDZ domain of NHERF1. These interactions were confirmed by surface plasmon resonance assays (K(D): 36 nM, 1.2 microM, and 41.7 microM, respectively). In vitro binding assays and co-immunoprecipitation studies revealed that the OAT4 wild-type but not a mutant lacking the PDZ motif interacted directly with both PDZK1 and NHERF1. OAT4, PDZK1, and NHERF1 proteins were shown to be localized at the apical membrane of renal proximal tubules. The association with PDZK1 or NHERF1 enhanced OAT4-mediated E1S transport activities in HEK293 cells (1.2- to 1.4-fold), and the deletion of the OAT4 C-terminal PDZ motif abolished this effect. The augmentation of the transport activity was accompanied by alteration in V(max) of E(1)S transport via OAT4 and was associated with the increased surface expression level of OAT4 protein. This study indicates that the functional activity of OAT4 is modulated through the PDZ interaction with the network of PDZK1 and NHERF1 and suggests that OAT4 is involved in the regulated apical organic anion handling in the renal proximal tubules, provided by the PDZ scaffold.
1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in Mycobacterium tuberculosis (2021)

This is the accepted manuscript version of the work published in its final form as Khonde, Lutete Peguy; Müller, Rudolf; Boyle, Grant A.; Reddy, Virsinha; Nchinda, Aloysius T.; Eyermann, Charles J.; Fienberg, Stephen; Singh, Vinayak; Myrick, Alissa; Abay, Efrem; Njoroge, Mathew; Lawrence, Nina; Su, Qin; Myers, Timothy G.; Boshoff, Helena I. M.; Barry, Clifton E.; Sirgel, Frederick A.; van Helden, Paul D.; Massoudi, Lisa M.; Robertson, Gregory T.; Lenaerts, Anne J.; Basarab, Gregory S.; Ghorpade, Sandeep R.; Chibale, Kelly. Journal of Medicinal Chemistry Volume: 64 issue: 17, page(s): 12790–12807. https://doi.org/10.1021/acs.jmedchem.1c00837 Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.
Evaluation and comparison of SuperLig{reg_sign} 644, resorcinol-formaldehyde and CS-100 ion exchange materials for the removal of cesium from simulated alkaline supernate (1995)

PNL evaluated three polymeric materials for Cs removal efficiency from a simulated Hanford Neutralized Current Acid Waste (NCAW) supernatant liquid using 200 mL ion exchange columns. Cs loadings (mmole Cs/g resin) were 0.20, 0.18, and 0.039 for Super Lig 644, R-F, and CS-100 (0.045, 0.070, 0.011 mmole Cs/mL resin). Elution of each resin material with 0.5 M HNO{sub 3} required 3.5, 7.0, and 3.2 cv to reach 0.1 C/C{sub 0} for the respective materials, resulting in volume compressions of 27, 20, and 6.9. Peak Cs concentrations during elution was 185, 38.5, and 27.8 C/C{sub 0}. SuperLig 644 had the highest Cs loading per gram in NCAW and the greatest volume compression on aci elution. Because of high density and poor elution, R-F had the highest Cs loading per unit volume and lower volume compression. CS-100, the baseline material for Cs removal at Hanford, was inferior to both SuperLig 644 and R-F in terms of Cs loading and selectivity over sodium.
Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells (2012)

Omega 3 fatty acids appear to enhance glycolytic, oxidative, and total metabolism. Moreover, both omega 3 and CLA treatment significantly increase mitochondrial content compared with control.
Hierarchical topic segmentation of websites (2006)

In this paper, we consider the problem of identifying and segmenting topically cohesive regions in the URL tree of a large website. Each page of the website is assumed to have a topic label or a distribution on topic labels generated using a standard classifier. We develop a set of cost measures characterizing the benefit accrued by introducing a segmentation of the site based on the topic labels. We propose a general framework to use these measures for describing the quality of a segmentation; we also provide an efficient algorithm to find the best segmentation in this framework. Extensive experiments on human-labeled data confirm the soundness of our framework and suggest that a judicious choice of cost measures allows the algorithm to perform surprisingly accurate topical segmentations.
Well-isolated L1 FePt–SiNx–C nanocomposite films with large coercivity and small grain size (2012)

FePt–SiNx–C films on TiN/CrRu/glass substrate with large coercivity, (001) texture, and small isolated grains were obtained by co-sputtering FePt, Si3N4, and C targets at 380 °C. It was found that when C was doped into the FePt–SiNx films, the out-of-plane coercivity increased while the small in-plane coercivity remained unchanged. Grain size decreased and grain size distribution became more uniform with increasing the C doping concentration. The x-ray photoelectron spectroscopy (XPS) depth profile showed a uniform depth distribution of Si in the FePt layer. The Si2p XPS spectrum implied the existence of Fe–Si bonds, indicating that SiNx was located at the FePt grain boundaries and was stable against diffusion to the surface, thus favoring grain isolation. Well-isolated FePt (001) granular films with coercivity higher than 21.5 kOe and an average grain size of 5.6 nm were obtained by doping 40 vol. % of SiNx and 20 vol. % of C.
Ultrasensitive Phototriggered Local Anesthesia (2017)

An injectable local anesthetic producing repeatable on-demand nerve block would be desirable for pain management. Here we present a phototriggerable device to achieve repeatable and adjustable on-demand local anesthesia in superficial or deep tissues, consisting of gold nanorods attached to low temperature sensitive liposomes (LTSL). The particles were loaded with tetrodotoxin and dexmedetomidine. Near-infrared light (NIR, 808 nm, continuous wave) could heat gold nanorods at low fluence (short duration and low irradiance), leading to rapid release of payload. In vivo, 1-2 min of irradiation at ≤272 mW/cm<sup>2</sup> produced repeatable and adjustable on-demand infiltration anesthesia or sciatic nerve blockade with minimal toxicity. The nerve block intensity and duration correlated with the irradiance and duration of the applied light.
Kinetics of uptake and effects of topical indomethacin application on protein concentration in the aqueous humor of dogs (1991)

The pharmacokinetic properties of indomethacin and its effects on aqueous protein values were studied in 15 clinically normal Beagles. The dogs were treated every 6 hours with 1% indomethacin suspension in 1 eye, with the other eye serving as a control. After 24 hours, the dogs were anesthetized and samples of aqueous humor (AH) were drawn by aqueocentesis at 0, 15, 30, 60, and 90 minutes after initial paracentesis. Additional samples were drawn at the time of euthanasia, 180 (6 dogs) and 360 minutes (9 dogs) minutes after initial paracentesis. Blood samples were obtained at each treatment and at each aqueocentesis. The eyes were enucleated after dogs were euthanatized. Aqueous protein concentrations and indomethacin concentrations in AH, plasma, and different ocular tissues were determined. Topical indomethacin administration had no effect on baseline protein concentrations of AH. It reduced protein concentrations in AH significantly at all times after initial aqueocentesis. This reduction was approximately 30%. Indomethacin in the AH is mostly protein-bound. Concentrations were 350 ng/ml in primary AH and 1,305 ng/ml in secondary AH, 90 minutes after initial aqueocentesis. Free-drug concentrations were relatively constant at about 220 ng/ml. Indomethacin administered topically is readily absorbed by the ocular adnexae, reaching a steady-state concentration of 25 ng/ml in blood plasma 18 hours after the start of treatment. Plasma concentrations were 50 times lower than therapeutically effective concentrations. High indomethacin concentrations were found in the cornea only. Low concentrations were found in the iris and ciliary body, the lens, and in the choroid.(ABSTRACT TRUNCATED AT 250 WORDS)
A novel graphite-like material of composition BC3, and nitrogen–carbon graphites (1986)

Interaction of benzene with boron trichloride at 800 °C yields a graphite-like metallic solid of composition BC3, and chlorine–pyridine mixtures at 800 °C give a nitrogen–carbon also having a graphite-like structure.
The Use of CIE for the Detection of Clostridium difficile Toxin in Stool Filtrates: Laboratory and Clinical Correlation (1983)

Two CIE procedures (CIE-1, CIE-2) for the detection of Clostridium difficile in diarrheal stools were evaluated by comparison to cytotoxin assay and culture results and by comparison to a clinical likelihood of C. difficile-induced diarrhea. Using a combination of toxin assay and culture results for reference, the CIE-1 and CIE-2 procedures had sensitivities of 33% and 47%, specificities of 89% and 91%, and positive predictive values of 42% and 54%, respectively. Using clinical likelihood for reference, the best results were obtained by the CIE-2 method, which yielded a positive predictive value of 77%. Neither CIE procedure provided an acceptable sensitivity for the detection of C. difficile in stools.
Unmanaged Networks IPv6 Transition Scenarios (2004)

This document defines the scenarios in which IPv6 transition mechanisms are to be used in networks. In order to evaluate the suitability of these mechanisms, we need to define the scenarios in which these mechanisms have to be used. One specific scope is the unmanaged network, which typically corresponds to a home or small office network. The scenarios are specific to a single subnet, and are defined in terms of IP connectivity supported by the gateway and the Internet Service Provider (ISP). We first examine the generic requirements of four classes of applications: local, client, peer to peer and server. Then, for each scenario, we infer transition requirements by analyzing the needs for smooth migration of applications from IPv4 to IPv6.
Multi-purpose generic board for hands-on power electronics education of different power converter topologies in PV applications (2018)

This paper presents the development of a multi-purpose generic board for hands-on power electronics education lab session focusing on Photovoltaic (PV) power electronics applications. The presented work tries to apply advanced methods for circuit designs and firmware developments of a DC/DC converter and a DC/AC converter for helping students to get familiar with system/subsystem level learning. The developed advanced converters can be used for interconnection of low voltage PV systems. Besides, the objective is to expedite the transferring of theory to practical purposes, and to provide hands-on experiences for the development of power electronics systems.
JEI Begins “e-First” Publication (2005)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.
Analytically useful blue chemiluminescence from a water-soluble iridium(iii) complex containing a tetraethylene glycol functionalised triazolylpyridine ligand (2016)

We examine [Ir(df-ppy)2(pt-TEG)](+) as the first highly water soluble, blue-luminescent iridium(III) complex for chemiluminescence detection. Marked differences in selectivity were observed between the new complex and the conventional [Ru(bpy)3](2+) reagent, which will enable this mode of detection to be extended to new areas of application.
The biosecurity benefits of genetic engineering attribution (2020)

Biology can be misused, and the risk of this causing widespread harm increases in step with the rapid march of technological progress. A key security challenge involves attribution: determining, in the wake of a human-caused biological event, who was responsible. Recent scientific developments have demonstrated a capability for detecting whether an organism involved in such an event has been genetically modified and, if modified, to infer from its genetic sequence its likely lab of origin. We believe this technique could be developed into powerful forensic tools to aid the attribution of outbreaks caused by genetically engineered pathogens, and thus protect against the potential misuse of synthetic biology.
The deubiquitinating enzyme USP7 regulates the transcription factor Nrf1 by modulating its stability in response to toxic metal exposure (2021)

The nuclear factor E2-related factor 1 (Nrf1) transcription factor performs a critical role in regulating cellular homeostasis as part of the cellular stress response and drives the expression of antioxidants and detoxification enzymes among many other functions. Ubiquitination plays an important role in controlling the abundance and thus nuclear accumulation of Nrf1 proteins, but the regulatory enzymes that act on Nrf1 are not fully defined. Here, we identified ubiquitin specific protease 7 (USP7), a deubiquitinating enzyme, as a novel regulator of Nrf1 activity. We found that USP7 interacts with Nrf1a and TCF11-the two long protein isoforms of Nrf1. Expression of wildtype USP7, but not its catalytically defective mutant, resulted in decreased ubiquitination of TCF11 and Nrf1a, leading to their increased stability and increased transactivation of reporter gene expression by TCF11 and Nrf1a. In contrast, knockdown or pharmacologic inhibition of USP7 dramatically increased ubiquitination of TCF11 and Nrf1a and reduction of their steady state levels. Loss of USP7 function attenuated the induction of Nrf1 protein expression in response to treatment with arsenic and other toxic metals, and inhibition of USP7 activity significantly sensitized cells to arsenic treatment. Collectively, these findings suggest that USP7 may act to modulate abundance of Nrf1 protein to induce gene expression in response to toxic metal exposure.
Albumin Binding, Relaxivity, and Water Exchange Kinetics of the Diastereoisomers of MS-325, a Gadolinium(III)-Based Magnetic Resonance Angiography Contrast Agent (2007)

The amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 consists of two slowly interconverting diastereoisomers, A and B (65:35 ratio), which can be isolated at pH > 8.5 (TyeklAr, Z.; Dunham, S. U.; Midelfort, K.; Scott, D. M.; Sajiki, H.; Ong, K.; Lauffer, R. B.; Caravan, P.; McMurry, T. J. Inorg. Chem. 2007, 46, 6621-6631). MS-325 binds to human serum albumin (HSA) in plasma resulting in an extended plasma half-life, retention of the agent within the blood compartment, and an increased relaxation rate of water protons in plasma. Under physiological conditions (37 degrees C, pH 7.4, phosphate buffered saline (PBS), 4.5% HSA, 0.05 mM complex), there is no statistical difference in HSA affinity or relaxivity between the two isomers (A 88.6 +/- 0.6% bound, r1 = 42.0 +/- 1.0 mM(-1) s(-1) at 20 MHz; B 90.2 +/- 0.6% bound, r1 = 38.3 +/- 1.0 mM(-1) s(-1) at 20 MHz; errors represent 1 standard deviation). At lower temperatures, isomer A has a higher relaxivity than isomer B. The water exchange rates in the absence of HSA at 298 K, kA298 = 5.9 +/- 2.8 x 10(6) s(-1), kB298 = 3.2 +/- 1.8 x 10(6) s(-1), and heats of activation, DeltaHA = 56 +/- 8 kJ/mol, DeltaHB = 59 +/- 11 kJ/mol, were determined by variable-temperature 17O NMR at 7.05 T. Proton nuclear magnetic relaxation dispersion (NMRD) profiles were recorded over the frequency range of 0.01-50 MHz at 5, 15, 25, and 35 degrees C in a 4.5% HSA in PBS solution for each isomer (0.1 mM). Differences in the relaxivity in HSA between the two isomers could be attributed to the differing water exchange rates.
Protection by tropolones against H2O2-induced DNA damage and apoptosis in cultured Jurkat cells (2005)

Tropolones, the naturally occurring compounds responsible for the durability of heartwood of several cupressaceous trees, have been shown to possess both metal chelating and antioxidant properties. However, little is known about the ability of tropolone and its derivatives to protect cultured cells from oxidative stress-mediated damage. In this study, the effect of tropolones on hydrogen peroxide-induced DNA damage and apoptosis was investigated in cultured Jurkat cells. Tropolone, added to the cells 15 min before the addition of glucose oxidase, provided a dose dependent protection against hydrogen peroxide induced DNA damage. The IC50 value observed was about 15 microM for tropolone. Similar dose dependent protection was also observed with three other tropolone derivatives such as trimethylcolchicinic acid, purpurogallin and beta-thujaplicin (the IC50 values were 34, 70 and 74 microM, respectively), but not with colchicine and tetramethyl purpurogallin ester. Hydrogen peroxide-induced apoptosis was also inhibited by tropolone. However, in the absence of exogenous H2O2 but in the presence of non-toxic concentrations of exogenous iron (100 microM Fe3+), tropolone dramatically increased the formation of single strand breaks at molar ratios of tropolone to iron lower than 3 to 1, while, when the ratio increased over 3, no toxicity was observed. In conclusion, the results presented in this study indicate that the protection offered by tropolone against hydrogen peroxide-induced DNA damage and apoptosis was due to formation of a redox-inactive iron complex, while its enhancement of iron-mediated DNA damage at ratios of [tropolone]/[Fe3+] lower than 3, was due to formation of a lipophilic iron complex which facilitates iron transport through cell membrane in a redox-active form.
Doppler ultrasound imaging of magnetically vibrated brachytherapy seeds (2003)

Vibration induced by an alternating magnetic field is proposed as a method for the identification of modified brachytherapy seeds with Doppler ultrasound. In vitro experiments with agar and liver-tissue phantoms using a clinical scanner and simple apparatus demonstrate that the technique is feasible.
Helping Children to Learn About Safer Sexual Behaviour (2017)

This unique resource comprises a therapeutic workbook and storybook, designed to be used as an early intervention with children within the school setting who display concerning sexual behaviour. The workbook contains a series of activities with accompanying user-friendly advice including how to broach difficult subjects, how to engage with children who have additional needs and how to create conditions of safety to enable the necessary conversations and activities to happen.&nbsp; The programme of work culminates in the creation of a unique and dynamic Safety Plan which is developed collaboratively with the child (as the expert) together with key adults in their lives. The Safety Plan is designed to meet the needs of the child and gives attention to their cultural context and specific likes/interests; this ultimately keeps them and other children safe from further incidents or allegations of sexually concerning behavior. The accompanying storybook, 'Billy and the Tingles' employs narrative therapy, telling the story of a child with sexually concerning behaviour and addressing contemporary issues of exposure to pornography. Laura Walker is a Senior Practitioner in a specialist service working with young people aged 7-17 years old who have displayed sexually concerning/harmful behavior. Laura has been a qualified Social Worker for 15 years with a background in child protection, fostering and sexual abuse work. Laura is currently studying for a Masters in Trauma Studies specialising in the relationship between trauma and sexually concerning behaviour in children. Carol Laugharneis a Practitioner in a specialist service working with young people aged 7-17 years old who have displayed sexually concerning/harmful behavior. Carol is a qualified Youth Worker with 20 years background in a number of settings with children and young people aged 4 - 19 years including Youth Work, Children's Rights, Drug and Alcohol Services, sexual exploitation and children of drug and alcohol using parents.