gebhart/patrepeval huggingface dataset:
Estrogen-Related Receptors as Emerging Targets in Cancer and Metabolic Disorders (2006)

While estrogen receptor (ER)-targeted therapeutics have clearly been a success in the treatment of breast cancer, the orphan estrogen-related receptors (ERRs) represent novel targets for future development. The ERRs, comprising ERRalpha, ERRbeta and ERRgamma, bind and regulate transcription via estrogen response elements (EREs) and extended ERE half-sites termed ERR response elements (ERREs), but do not bind endogenous estrogens. The emerging role of ERRalpha and ERRgamma in modulating estrogen responsiveness, substituting for ER activities, and serving as prognosticators in breast and other cancers is providing an impetus for the identification of compounds which target these proteins. Moreover, ERRalpha plays a role in energy homeostasis and will likely be targeted for the treatment of metabolic disorders. Multiple classes of synthetic ligands have already been identified. The phytoestrogens genistein, daidzein, biochanin A and 6,3'4'-tryhydroxyflavone have been reported as ERRalpha agonists. The phenolic acyl hydrazones GSK4716 and GSK9089 act as selective agonists of ERRbeta and ERRgamma. The organochlorine pesticides toxaphene and chlordane, and the synthetic compound XCT790 antagonize ERRalpha. The synthetic estrogen diethylstilbestrol antagonizes all three ERRs. The selective estrogen receptor modulators 4-hydroxytamoxifen and 4-hydroxytoremifene antagonize ERRgamma. The rational development of synthetic ligands for the ERRs may soon provide new agents to supplement the repertoire of antihormonal therapies to combat breast cancer. Moreover, expression of ERRs in other cancers and metabolic disorders may provide a targeted treatment strategy for these patients as well.
Isoniazid Proliposome Powders for Inhalation—Preparation, Characterization and Cell Culture Studies (2011)

The aims of this study were to develop proliposome powders containing isoniazid (INH) in a dry powder aerosol form. INH-proliposome powders were prepared by a spray drying method. Proliposome physicochemical properties were determined using cascade impactor, X-ray diffraction and differential scanning calorimetry. The toxicity of proliposomes to respiratory-associated cell lines and its potential to provoke immunological responses from alveolar macrophages (AM) were determined. Free INH and INH-proliposome bioactivities were tested in vitro and in AM infected with Mycobacterium bovis (M. bovis). Aerosolization properties of INH-proliposome powders at 60 L/min, the powders showed mass median aerodynamic diameters of 2.99-4.92 μm, with fine particle fractions (aerosolized particles less than 4.4 μm) of 15-35%. Encapsulation of INH was 18-30%. Proliposome formulations containing INH to mannitol ratios of 4:6 and 6:4 exhibited the greatest overlapping peak between the drug and mannitol. INH-proliposomes were evidently nontoxic to respiratory-associated cells, and did not activate AM to produce inflammatory mediators-including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide-at a toxic level. The efficacy of INH-proliposome against AM infected with M. bovis was significantly higher than that of free INH (p < 0.05). INH-proliposomes are potential candidates for an alternative tuberculosis treatment.
P1–068: Synaptic and cognitive impairment in an amyloid–depositing mouse model after sildenafil treatment (2006)

Alzheimer's disease (AD) begins as a disorder of synaptic function, caused in part by increased levels of amyloid–β–peptide 1–42 (Aβ42). Both synaptic and cognitive deficits are reproduced in double transgenic mice for amyloid precursor protein (APP:K670N,M671L) and presenilin–1 (PS1:M146V) (Trinchese et al, Ann Neurol. 2004, 55:801), termed APP/PS1 mice. In fact, long–term potentiation (LTP), a cellular model of synaptic plasticity that might underlie learning and memory, and spatial working memory, are impaired at early stages in APP/PS1 animals. Previous studies showed that, when modulating hippocampal synaptic plasticity, Aβ downregulates the NO/cGMP/CREB memory pathway and enhancement of the NO/cGMP signaling may restore Aβ–induced LTP impairment and CREB phosphorylation (Puzzo et al, J Neurosci. 2005, 25:6887). To investigate whether a treatment with sildenafil, a compound that elevates cGMP levels by inhibiting phosphodiesterase 5, has a beneficial effect on synaptic and cognitive deficits in APP/PS1 mice. Basal synaptic transmission (BST) and LTP were recorded at the CA3–CA1 hippocampal connection. Contextual learning and spatial working memory were studied through fear conditioning and radial–arm water–maze, respectively. CREB phosphorylation was analyzed on slices used for electrophysiology. A brief 10 min application of sildenafil (1μM), synthesized as previously reported (Terrett et al, Bioorg Med Chem Lett. 1996, 6:1819), re–established normal potentiation and CREB phosphorylation in 3 month–old APP/PS1 slices. A single injection of sildenafil (3mg/kg, i.p.) also improved contextual and spatial working memory in the double transgenic mice. Sildenafil was also capable of maintaining its protective effect over a prolonged period of time. Both APP/PS1 and WT mice were injected with sildenafil (3 mg/kg/day, ip) for 3 weeks, then the treatment was stopped for 9–12 weeks prior to testing. Mice were next subjected to the radial–arm water–maze task and re–tested for contextual learning. Results revealed a strong effect of treatment in APP/PS1 mice treated with sildenafil compared to APP/PS1 animals treated with vehicle. Electrophysiological studies showed an improvement of both BST and LTP in sildenafil–treated APP/PS1 mice; immunocytochemistry for phospho–CREB confirmed the beneficial effect of sildenafil in the transgenic mice. Sildenafil treatment ameliorates synaptic and cognitive dysfunction in AD mouse model.
Parenteral Anticoagulation with the Heparinoid Lomoparan (Org 10172) in Patients with Heparin Induced Thrombocytopenia and Thrombosis (1992)

Progressive thrombocytopenia may develop in as many as 5% of patients receiving heparin anticoagulation. In these patients, the risk of thromboembolic complications as well as continued thrombocytopenia necessitates discontinuation of heparin and initiation of an alternative anticoagulant when indicated. The heparinoid Lomoparan (Org 10172) is a mixture of several non-heparin low molecular weight glycosaminoglycans with proven anticoagulant efficacy that is generally non-reactive with platelets in the presence of plasma from patients with heparin induced thrombocytopenia, whereas standard heparin will induce platelet aggregation. We evaluated the role of heparinoid as a potential alternative anticoagulant in patients with heparin induced thrombocytopenia. During a 6 month period, we identified six patients with heparin induced thrombocytopenia who required an alternative parenteral anticoagulant, four as primary treatment for specific medical problem, and two as anticoagulation during a necessary surgical procedure. Heparinoid was used successfully in both medical and surgical patients requiring parenteral anticoagulation. In no case was there an exacerbation of the thrombocytopenia nor thromboembolic complications while on heparinoid therapy. Three of our patients sustained hemorrhagic complications, predominantly in the post-surgical setting in association with elevated anti-factor Xa levels and additional anticoagulant agents. We feel that these results confirm the utility of heparinoid anticoagulation in a select subset of patients with heparin induced thrombocytopenia who require continued parenteral anticoagulation.
UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction (2018)

UMAP (Uniform Manifold Approximation and Projection) is a novel manifold learning technique for dimension reduction. UMAP is constructed from a theoretical framework based in Riemannian geometry and algebraic topology. The result is a practical scalable algorithm that applies to real world data. The UMAP algorithm is competitive with t-SNE for visualization quality, and arguably preserves more of the global structure with superior run time performance. Furthermore, UMAP has no computational restrictions on embedding dimension, making it viable as a general purpose dimension reduction technique for machine learning.
Copper(II)2(3,5-diisopropylsalicylate)4 stimulates hemopoiesis in normal and irradiated mice. (1988)

We have previously reported that copper(II)2(3,5-diisopropylsalicylate)4 (Cu-DIPS) significantly increased the survival rate of mice exposed to lethal irradiation. To examine whether Cu-DIPS affected hemopoietic activity, groups of mice were treated with Cu-DIPS or vehicle and assayed for in vitro interleukin 3 (IL-3)-dependent colony-forming units (CFU-C) and for committed progenitor granulocyte-macrophage CFU (GM-CFU). Cu-DIPS increased the number of splenic IL-3 CFU-C by five- to sixfold 7 days after treatment and splenic GM-CFU by 12-fold on day 24. These increases were accompanied by a 50% increase in spleen weight. Bone marrow IL-3 CFU-C and GM-CFU were not affected at 7 or 14 days after treatment, but were somewhat depressed at 24 days. In irradiated (8.0 Gy) mice treated with Cu-DIPS or vehicle, splenic IL-3 CFU-C and GM-CFU were undetectable 7 days after irradiation, but recovered more rapidly in Cu-DIPS-treated mice. By 24 days splenic IL-3 CFU-C in Cu-DIPS-treated mice recovered to 150% of normal (unirradiated) values and GM-CFU recovered to 270% of normal, whereas irradiated control values remained at 25% and 7%, respectively. The recovery of bone marrow hemopoiesis was slower than spleen, but 42 days after irradiation Cu-DIPS-treated mice had higher levels of bone marrow IL-3 CFU-C (eightfold) and GM-CFU (4.6-fold) than vehicle-treated mice. Cu-DIPS stimulated sixfold increases in renewable, pluripotent stem cells as measured by the in vivo assay of endogenous colony-forming units (CFU-Se).
Plasma vascular endothelial growth factor is useful in assessing progression of breast cancer post surgery and during adjuvant treatment (2002)

Vascular endothelial growth factor (VEGF) has been shown to induce angiogenesis in vivo and in vitro. However, the association of plasma VEGF with tumor histopathology in high risk groups such as African American and non-white Hispanic women with breast cancer is not well understood. There is limited information on the prognostic relevance of plasma VEGF in patients who have had surgery and adjuvant treatment for breast cancer. In this study, we measured plasma VEGF from 125 minority women with primary breast tumor removal and were completing adjuvant treatment. The control group consisted of 20 subjects without cancer. We examined the association between plasma VEGF and other tumor characteristics such as steroid hormone receptors, tumor size, regional nodes, stage, recurrence, and overall survival. Our results confirmed that plasma VEGF levels were significantly higher in breast cancer patients than normal subjects. Plasma VEGF level increased in patients with increase in tumor size, and at late stage III/IV disease. Univariate analysis showed plasma VEGF to be a significant predictor of overall survival (RR=2.5, p=0.02). Multivariate analysis showed plasma VEGF not only to be an independent predictor of overall survival (RR=4.6, p=0.02) but also of local recurrence (RR=6.0, p=0.04). Tamoxifen in combination with CMF or CAF can reduce plasma VEGF level in patients with estrogen receptor positive tumor but not in estrogen receptor negative tumor. Our findings suggest that plasma VEGF should be considered as a tumor marker for breast cancer progression, and inhibitors of angiogenesis should be factored into the treatment protocol for patients who demonstrate increase in plasma VEGF levels at any stage of the disease.
Wideband communications in the high frequency band using direct sequence spread spectrum with error control coding (2002)

For the last decade or so, major developments in the fields of large scale integration (LSI) and digital signal processing (DSP) technologies have brought forward promising techniques to increase the transmitted data rate over the HF sky-wave channel. The lack of processing power restricting HF systems to low transmission rates has long been overcome and the potential of spread spectrum (SS) technologies for resolving multipath returns may now be better exploited. A wideband HF sky-wave channel model, based on the Ionospheric Parameters Model (IPM) has been implemented in software and is used to demonstrate the potential of direct sequence (DS) spread spectrum over wideband HF channels. New performance results of a RAKE receiver-based system are presented and conclusions regarding its most promising configuration with Reed-Solomon and convolutional codes are advanced in terms of improved channel reliability and transmission rate.
Tumour vascular disrupting agents: combating treatment resistance (2008)

A large group of tubulin-binding microtubule-depolymerizing agents act as tumour vascular disrupting agents (VDAs). Several members of this group are now in clinical trials in combination with conventional anticancer drugs and radiotherapy. Here we briefly update on the development of tubulin-binding combretastatins as VDAs, summarize what is known of their mechanisms of action and address issues relating to treatment resistance, using disodium combretastatin A-4 3-O-phosphate (CA-4-P) as an example. Characteristically, VDAs cause a rapid shutdown of blood flow to tumour tissue with much less effect in normal tissues. However, the tumour rim is relatively resistant to treatment. Hypoxia (or hypoxia reoxygenation) induces upregulation of genes associated with angiogenesis and drug resistance. It may be possible to take advantage of treatment-induced hypoxia by combining with drugs that are activated under hypoxic conditions. In summary, VDAs provide a novel approach to cancer treatment, which should effectively complement standard treatments, if treatment resistance is addressed by judicious combination treatment strategies.
Adipic Acid (2003)

Abstract Adipic acid, hexanedioic acid, 1,4‐butanedicarboxylic acid, mol wt 146.14, HOOCCH 2 CH 2 CH,CH 2 COOH, is a white crystalline solid with a melting point of about 152°C. Little of this dicarboxylic acid occurs naturally, but it is produced on a very large scale at several locations around the world. The majority of this material is used in the manufacture of Nylon‐6,6 polyamide, which is prepared by reaction with 1,6‐hexanediamine. Adipic acid is a colorless, odorless, sour‐tasting crystalline solid that undergoes reactions including esterification, amidation, reduction, halogenation, salt formation, and dehydration. It also undergoes several industrially significant polymerization reactions. Adipic acid historically has been manufactured predominantly from cyclohexane. However, much research continues to be directed to alternative feedstocks, especially butadiene and cyclohexene, as dictated by shifts in hydrocarbon pricing. Air quality regulations may exert further pressure for alternative routes as manufacturers seek to avoid NO x abatement costs. When dispersed as a dust, adipic acid is subject to normal dust explosion hazards. The material is an irritant, especially upon contact with the mucous membranes. Protective goggles or face shields should be worn when handling the material. The material should be stored in corrosion‐resistant containers, away from alkaline or strong oxidizing materials. Adipic acid is a very large‐volume organic chemical and is one of the top 50 chemicals produced in the United States in terms of volume, although demand is highly cyclic. Adipic acid for nylon takes ∼60% of U.S. cyclohexane production. Adipic acid is relatively nontoxic.
Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6 (2011)

These data suggest that LPS can directly activate the brain endothelium even at relatively low doses, obviating the need for systemic cytokine stimulation to transduce systemic inflammatory signals into the brain or to exacerbate existing pathology.
Multimode antenna selection for spatial multiplexing systems with linear receivers (2005)

Spatial multiplexing is a simple transmission technique for multiple-input multiple-output (MIMO) wireless communication links in which data is multiplexed across the transmit antennas. In Rayleigh fading matrix channels, however, spatial multiplexing with low-complexity linear receivers suffers due to a lack of diversity advantage. This paper proposes multimode antenna selection, which uses a low-rate feedback channel to improve the error rate performance of spatial multiplexing systems with linear receivers. In the proposed technique, both the number of substreams and the mapping of substreams to antennas are dynamically adjusted, for a fixed total data rate, to the channel based on limited feedback from the receiver. Dual-mode selection, where spatial multiplexing or selection diversity is adaptively chosen, dramatically improves the diversity gain achieved. Multimode selection (i.e., allowing any number of substreams to be dynamically selected) provides additional array gain. Various criteria for selecting the number of substreams and the optimal mapping of substreams to transmit antennas are derived. Relationships are made between the selection criteria and the eigenmodes of the channel. A probabilistic analysis of the selection criteria are provided for Rayleigh fading channels. Applications to nonlinear receivers are mentioned. Monte Carlo simulations demonstrate significant performance improvements in independent and identically distributed (i.i.d.) flat-fading Rayleigh matrix channels with minimal feedback.
11B NMR Probes of Copper(II): Finding and Implications of the Cu2+‐Promoted Decomposition of ortho‐Carborane Derivatives (2016)

Abstract The development of noninvasive methodologies for the detection of d‐block metal ions such as copper (Cu 2+ ), zinc (Zn 2+ ), and manganese (Mn 2+ ) is important for understanding their biological roles and relationship with diseases. We have been interested in the use of 11 B NMR probes for the detection of d‐block metal ions, because 11 B is an ultratrace element in living systems. o ‐Carboranes, which consist of ten boron and two carbon atoms, have been applied to numerous drugs and biological active agents. In this work, we found that the o ‐carborane‐pendant cyclens (L 3 –L 5 ) (cyclen = 1,4,7,10‐tetraazacyclododecane) are decomposed in the presence of Mn 2+ or Cu 2+ in aqueous solution at neutral pH, accompanied by the release of 4–9 equiv. of B(OH) 3 . Furthermore, it was found that o ‐carborane derivatives that contain hydroxyl groups instead of a cyclen unit also undergo decomposition in the presence of Cu 2+ and the corresponding complexes such as Cu(bpy) to afford 10 equiv. of B(OH) 3 , as confirmed by 11 B NMR spectroscopic analysis and an azomethine‐H assay. These reactions are applied to 11 B MRI (magnetic resonance imaging) probes for Cu 2+ .
Taxol plus recombinant human granulocyte-colony stimulating factor as initial and as salvage chemotherapy for metastatic breast cancer: a preliminary report. (1993)

Twenty-eight patients received Taxol as their first chemotherapy for stage IV breast cancer. An additional 51 patients with extensive prior exposure to other chemotherapeutic agents received Taxol as salvage therapy. We found significant activity for the drug in both situations, as well as a strong clinical suggestion of non-cross-resistance with doxorubicin. An excellent response in previously irradiated skin was noted in one case. The routine use of recombinant human granulocyte-colony stimulating factor seemed to ameliorate some of the dose-limiting toxicity of neutropenia. Other toxicity was mild to moderate in most cases. With further development, Taxol should play a significant role in the systemic management of breast cancer.
An algorithm for multisource beamforming and multitarget tracking (1996)

A new algorithm for simultaneous robust multisource beamforming and adaptive multitarget tracking is proposed. Self-robustness to locations errors or variations is introduced by a source-subspace-based tracking procedure of steering vectors in the array manifold. This LMS-type procedure is generalized from a former work we developed in the single source case. Two beamforming structures are actually proposed. The first is adaptive and optimal for uncorrelated sources and correlated noise. The second is conventional and optimal for correlated sources and uncorrelated white noise. The proposed algorithm and MUSIC show an identical asymptotic variance in localization for immobile sources, whereas for the mobile case, the proposed algorithm is highly advantageous. Then, it is shown that the additional use of some kinematic parameters (i.e., speed, acceleration, etc.) inferred from the reconstructed trajectories improves the tracking performance and overcomes some of the problems of crossing targets. The efficiency of multitarget tracking and the robustness of multisource beamforming are proved and then confirmed by simulation. The number of sources can be initialized and tracked by a marginal proposed procedure. The beamforming performance is shown to be optimal as the single source case. Finally, the algorithm has a very low order of arithmetic complexity.
Pigs Express Multiple Forms of Decay-Accelerating Factor (CD55), All of Which Contain Only Three Short Consensus Repeats (2000)

We report the cloning of cDNAs encoding multiple isoforms of the pig analogue of human decay-accelerating factor (DAF; CD55). Screening of a pig muscle cDNA library using a human DAF probe identified a single clone that encoded a DAF-like molecule comprising three short consensus repeats (SCR) homologous with the amino-terminal three SCR in human DAF, a serine/threonine-rich (ST) region, and sequence compatible with a transmembrane domain and cytoplasmic tail. Northern blot and RT-PCR analysis showed that pig DAF was expressed in a wide range of tissues. Additional isoforms of DAF were sought using RT-PCR and 3'-rapid amplification of cDNA ends followed by sequencing. Isoforms containing a GPI anchor and with differing lengths of ST region were identified; no isoform containing a fourth SCR was found. Cloning of the GPI-anchored isoform from granulocytes confirmed that it was identical with the original transmembrane isoform through the three SCR and first portion of ST and was derived from a frame shift caused by splicing out 176 bp of sequence. A panel of mAbs was generated and used to analyze the distribution and anchoring of pig DAF in circulating cells. Pig DAF was expressed on all circulating cells and was transmembrane anchored on erythrocytes, but completely or partially GPI anchored on granulocytes and mononuclear cells. The transmembrane isoform of pig DAF was expressed on Chinese hamster ovary cells and was shown to affect regulatory activity for the classical pathway of human complement, but was only marginally active against pig serum.