gebhart/patrepeval huggingface dataset:
Abstract C60: Pre-clinical efficacy of the ATR inhibitor AZD6738 in combination with the PARP inhibitor olaparib (2015)

Abstract The PARP inhibitor olaparib acts through both inhibition of DNA single-strand-break repair and trapping of PARP-DNA complexes creating DNA lesions which cause replication fork stalling and collapsed fork DNA breaks. Cells which have lost BRCA-dependent homologous recombination repair are highly sensitive to olaparib treatment and this has led to its approval in patients with tumors carrying BRCA mutations. In addition, ATM (Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia mutated and Rad3 related) dependent DNA repair processes are hypothesized to be important survival pathways to PARP inhibitor treatment. In pre-clinical studies cancer cells which have defects in either ATM or ATR have been shown to be sensitive to PARP inhibitors. Here we present data that the orally bioavailable ATR inhibitor AZD6738 (in Phase-I clinial trials) combines synergistically with olaparib leading to cell death and anti-tumour activity in pre-clinical models. The combinations are effective across a panel of gastric and lung cancer cell lines in vitro. In addition results from isogenic ATM−/-/− knockout versus ATM+/+/+FaDu head and neck cancer cell line pairs show enhanced combination activity in ATM knockout cells versus ATM wild-type cells. Studies in vivo show that through intermittent dosing the combination is tolerated while demonstrating significant anti-tumour efficacy and regressions across multiple human patient derived primary explant models. Together, these data support the notion of development of AZD6738 and olaparib combinations for the treatment of ATM-deficient cancers. Citation Format: Alan Lau, Elaine Brown, Andrew Thomason, Rajesh Odedra, Victoria Sheridan, Elaine Cadogan, Shirlian Xu, Andy Cui, Paul R. Gavine, Mark O'Connor. Pre-clinical efficacy of the ATR inhibitor AZD6738 in combination with the PARP inhibitor olaparib. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C60.
A high-performance integrated K-band diplexer (1999)

This paper describes the design and measurement of a planar diplexer integrated on a single silicon substrate. The diplexer channels are 5% and 6.5% relative bandwidth at 28 and 31 GHz, respectively. The diplexer is based on a micropackaged membrane supported capacitively coupled microstrip structure and is 1.5 cm/spl times/1.6 cm and only 1.4 mm thick. The measured insertion loss is 1.4 dB (5%) and 0.9 dB (6.5%) for the two channels with better than 35 dB isolation in the 28 GHz band and better than 50 dB isolation in the 31 GHz band. The measured results include all transition and packaging effects. The diplexer has coplanar-waveguide ports and can easily be integrated with other elements such as planar antennas, low-noise amplifier, and power amplifiers.
Efficacy and Safety of Treprostinil: An Epoprostenol Analog for Primary Pulmonary Hypertension (2003)

Intravenous epoprostenol is currently FDA approved for management of primary pulmonary hypertension, but it requires intravenous infusion and is associated with adverse effects. The objective of this study was to evaluate the effects of an epoprostenol analog, treprostinil, for management of pulmonary hypertension. Ten tertiary care academic institutions with pulmonary hypertension programs participated in these pilot trials. In the first trial, intravenous epoprostenol and intravenous treprostinil were compared. In the second trial, intravenous treprostinil and subcutaneous treprostinil were compared. In the third trial, subcutaneous treprostinil was compared with placebo infusion during an 8-week period. Intravenous epoprostenol and intravenous treprostinil resulted in a similar reduction in pulmonary vascular resistance acutely (22% and 20%, respectively). Intravenous treprostinil and subcutaneous treprostinil also demonstrated comparable short-term decrease in pulmonary vascular resistance (23% and 28%, respectively). The placebo-controlled 8-week trial demonstrated a mean improvement of 37 +/- 17 m as measured by the 6-minute walk distance in patients receiving treprostinil compared with a 6 +/- 28 m reduction in those receiving placebo. There were trends toward an improvement in cardiac index and pulmonary vascular resistance index in the treprostinil group. Subcutaneous treprostinil has favorable hemodynamic effects when given acutely and in the short term. Treprostinil can be given safely to an ambulatory patient with a novel subcutaneous delivery pump system.
Scene Coordinate Regression Forests for Camera Relocalization in RGB-D Images (2013)

We address the problem of inferring the pose of an RGB-D camera relative to a known 3D scene, given only a single acquired image. Our approach employs a regression forest that is capable of inferring an estimate of each pixel's correspondence to 3D points in the scene's world coordinate frame. The forest uses only simple depth and RGB pixel comparison features, and does not require the computation of feature descriptors. The forest is trained to be capable of predicting correspondences at any pixel, so no interest point detectors are required. The camera pose is inferred using a robust optimization scheme. This starts with an initial set of hypothesized camera poses, constructed by applying the forest at a small fraction of image pixels. Preemptive RANSAC then iterates sampling more pixels at which to evaluate the forest, counting inliers, and refining the hypothesized poses. We evaluate on several varied scenes captured with an RGB-D camera and observe that the proposed technique achieves highly accurate relocalization and substantially out-performs two state of the art baselines.
A mimotope peptide‐based vaccine against Schistosoma mansoni: synthesis and characterization (2000)

A panel of four mimotopes of the epitope recognized by the highly protective monoclonal antibody against Schistosoma mansoni (152-66-9B) was obtained by screening a solid-phase 8mer random peptide library. Three of the four mimotopes (p28, p29 and p30) were efficiently recognized in an in vitro radioimmunoassay by the monoclonal antibody and by sera from infected mice and one (p30) induced in vitro proliferation of primed lymphocytes. When the mimotopes were conjugated to bovine serum albumin (BSA) and the conjugates used to immunize C57BL/6J mice, only the p30-BSA-induced antibodies which were effective at complement-mediated killing of schistosomula. The level of complement-mediated killing obtained with the anti-p30 antibodies was comparable to that seen with serum from mice immunized with the protective 9B-antigen. Furthermore, following challenge infection of mimotope-BSA-immunized mice, a greater than 40% reduction in worm burden was observed in p30-BSA-immunized mice, a level comparable to that seen following immunization with the intact 9B-antigen. These results show that a simple synthetic peptide immunogen comprising an eight-amino acid mimotope of a conformational epitope on the 9B-antigen can induce protective immune responses against S. mansoni that are comparable to those obtained following immunization with the far more complex intact antigen. This mimotope may well represent a potential component of a synthetic peptide vaccine against S. mansoni. The inclusion of other B-cell- and T-cell-stimulating synthetic epitopes in such a vaccine, together with a more appropriate carrier, adjuvant and delivery systems may well result in a level of protection even greater than that seen with the single mimotope.
Liver X receptors as potential targets for cancer therapeutics (Review) (2017)

Liver X receptors (LXRs) are important members of the nuclear receptor family that were originally determined to function in cholesterol transport and the regulation of immune responses. Synthetic LXR ligands have been developed to treat various diseases including diabetes, Alzheimer's disease and atherosclerosis. Previous studies have suggested that LXRs are also involved in numerous types of cancer and are therefore potential targets for cancer therapeutics. The present review summarizes LXR ligands and their mechanisms of action, the effects of LXRs in different types of cancer and their potential applications in clinical treatment. Together, the studies discussed in the present review indicate that LXRs may be potential targets for cancer therapeutics.
Wireless reconfigurable modules for robotic endoluminal surgery (2009)

In this paper, a reconfigurable modular robotic system is proposed to augment the dexterity of endoluminal interventions in the gastrointestinal tract. In the proposed system, miniaturized robotic modules are ingested and assembled in the stomach cavity. The assembled robot can change its configuration according to the target location, thus enabling complicated surgical tasks. The robotic assembly, the robotic configuration and the surgical tasks are controlled via wireless bidirectional communication. Based on this concept, early prototypes of the robotic modules were designed and fabricated. The developed module has 2DOF (±90° of bending and 360° of rotation), measures 15.4 mm in diameter and 36.5 mm in length. It weighs 5.6 g and contains a Li-Po battery, two brushless DC motors, and a custom-made control board capable of wireless communication. The performance of the bending and rotational motion was evaluated and the future work has been discussed.
Faster algorithms for the shortest path problem (1990)

Efficient implementations of Dijkstra's shortest path algorithm are investigated. A new data structure, called the radix heap , is proposed for use in this algorithm. On a network with n vertices, m edges, and nonnegative integer arc costs bounded by C , a one-level form of radix heap gives a time bound for Dijkstra's algorithm of O ( m + n log C ). A two-level form of radix heap gives a bound of O ( m + n log C /log log C ). A combination of a radix heap and a previously known data structure called a Fibonacci heap gives a bound of O ( m + n a @@@@log C ). The best previously known bounds are O ( m + n log n ) using Fibonacci heaps alone and O ( m log log C ) using the priority queue structure of Van Emde Boas et al. [ 17].
DEVELOPMENT OF AN IN-HOUSE AUTOMATED VEHICLE LOCATION SYSTEM (2003)

Students, faculty and staff at the University of Illinois at Chicago (UIC) must move around a campus that is approximately two miles from east to west and one mile from north to south, and that continues to expand. A free shuttle bus service is a primary mode of transportation. In order to enhance the user experience, and ultimately the service, a GPS-based monitoring system is being developed. Because of limited resources, staff in the UIC Facilities Department and the Urban Transportation Center devised a way to create a low-cost system built with “off-the shelf” hardware. The system’s data is mapped on a public website so that users can 1) gain greater awareness of the bus routes and 2) determine the wait time until the next bus would arrive at their stop. A secondary potential benefit of the system (after full implementation) is that it should allow for better operations management due to its ability to accurately locate buses. Currently, communications management with buses is achieved via two-way radios and supervisor oversight. Implementation involved the installation of the hardware on each of the ten shuttle buses on the campus. The hardware on each bus included: a commercially available GPS locator, modem and two-way radio. An antenna was also installed on the highest building on campus (30 stories) to transmit the data. The data is transmitted at 15-second intervals over a publicly available radio frequency.
Envelhecimento facial: perda de volume e reposição com ácido hialurônico (2010)

Facial aging is a consequence of multiple, interacting intrinsic and extrinsic factors that contributes importantly to the skin changes as wrinkles, brown spots, loss of elasticity, and others. Volume deficits resulting from the loss and repositioning of facial fat, as well as from skeletal remodeling, are now considered as a fundamental component of facial aging. With these changes, the convexities typical of a youthful appearance tend to flatten and droop. Facial rejuvenation has moved beyond wrinkle effacement and surgical facelifts to an approach that relaxes muscles and volumizes, shapes, recontours, and retexturizes. This paper reports adapted techniques to achieve facial revolumization rejuvenation using high viscosity hyaluronic acid gel in subdermal place
Targeted Iron Oxide Nanocomplex as a Theranostic Agent for Cancer (2011)

Currently there are no tumor-specific superparamagnetic iron oxide (SPIO) nanocomplexes on the market for use as either diagnostic or hyperthermic agents. Moreover, none of the current hyperthermia approaches can efficiently treat disseminated (metastatic) cancer. Our antitransferrin receptor scFv immunoliposome (scL) is a systemically administered, tumor-targeting nanocomplex for molecular medicines. It efficiently and specifically delivers various payloads to tumor cells in vivo and has successfully completed a phase I clinical trial for p53 gene therapy. We modified this scL complex to encapsulate SPIO. We have demonstrated that the scL nanocomplex can deliver SPIO specifically and efficiently into tumor cells, resulting in tumor growth inhibition in vivo. Thus, scL-SPIO should be capable of delivering sufficient SPIO to generate therapeutic temperatures only in the tumor when the patient is exposed to an alternating magnetic field. As SPIO is also used in MRI, use of scL-SPIO would allow simultaneous imaging and hyperthermic treatment. This scL-SPIO nanocomplex theranostic agent has the potential to simultaneously diagnose metastatic tumors, act as a therapeutic, and assess the treatment effect while minimizing heat effects on normal cells. Thus, it could have a significant clinical impact on the treatment of cancer, including metastatic lung cancer.
The neurochemical and behavioral effects of the novel cholinesterase–monoamine oxidase inhibitor, ladostigil, in response to L‐dopa and L‐tryptophan, in rats (2005)

The novel drugs, ladostigil (TV3326) and TV3279, are R and S isomers, respectively, derived from a combination of the carbamate cholinesterase (ChE) inhibitor, rivastigmine, and the pharmacophore of the monoamine oxidase (MAO) B inhibitor, rasagiline. They were developed for the treatment of comorbidity of dementia with Parkinsonism. In the present study, we determined the effects of these drugs on both aminergic neurotransmitter levels and motor behavioral activity in naïve and in L-dopa- or L-tryptophan-induced rats. Chronic treatment of rats with ladostigil (52 mg kg(-1) for 21 days) inhibited hippocampal and striatal MAO A and B activities by >90%, increased striatal levels of dopamine and serotonin, and inhibited striatal ChE activity by approximately 50%. Chronic TV3279 (26 mg kg(-1) for 21 days) similarly inhibited approximately 50% of striatal ChE activity, but did not affect MAO activity or amine levels. In sharp contrast to the inductive effect of the MAO A/B inhibitor, tranylcypromine (TCP), on stereotyped hyperactivity in response to L-dopa (50 mg kg(-1)) or L-tryptophan (100 mg kg(-1)), ladostigil completely inhibited these behavioral hyperactivity syndromes. Accordingly, acute rivastigmine (2 mg kg(-1)) and chronic TV3279 abolished the ability of TCP to initiate L-dopa-induced hyperactivity, while scopolamine (0.5 mg kg(-1)) reversed the inhibitory effect of chronic ladostigil on L-dopa-induced hyperactivity, suggesting that ladostigil may attenuate successive locomotion by activating central cholinergic muscarinic receptors.Finally, while chronic ladostigil administration to naïve rats resulted in preserved spontaneous motor behavior, acute treatment with ladostigil decreased motor performance, compared to control animals. In contrast, chronic as well as acute treatments with TV3279 reduced spontaneous motor activity. Thus, the aminergic potentiation by ladostigil may counteract its cholinergic inhibitory effect on spontaneous motor behavior. Our results suggest that potentiation of both aminergic and cholinergic transmission systems by ladostigil contributes equally to motor behavior performance, which is substantially impaired in comorbidity of dementia with Parkinsonism including dementia with Lewy bodies (DLB).
Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice (1997)

Genetic crosses produced NOD/LtSz mice doubly homozygous for the severe combined immunodeficiency (scid) mutation and the beta2m (B2m) null allele. Both NOD/LtSz-scid/scid and NOD/LtSz-scid/scid B2m(null) mice lacked mature lymphocytes and serum Ig. However, homozygosity for the B2m(null) allele also resulted in the absence of MHC class I expression, loss of NK cell activity, accumulation of iron in the liver, and rapid clearance of human IgG1. NOD/LtSz-scid/scid B2m(null) mice supported markedly elevated levels of human T cell engraftment, compared with NOD/LtSz-scid/scid control animals, following injection with human PBMC. The increased engraftment was associated with a major increase in the number of human CD4+ T cells. Following injection with 20 million human PBMC, levels of human CD4+ T cells in the peripheral blood and spleen of NOD/ LtSz-scid/scid B2m(null) mice were 6- to 7-fold higher than those in NOD/LtSz-scid/scid mice and >50-fold higher than those in C.B-17-scid/scid mice. The resulting normalization of CD4+/CD8+ ratios in NOD/LtSz-scid/scid B2m(null) mice is in sharp contrast to that observed in NOD/LtSz-scid/scid mice or in C.B-17-scid/scid mice. Circulating human IgG was cleared 6-fold more rapidly in NOD/LtSz-scid/scid B2m(null) mice than in NOD/LtSz-scid/scid mice. This rapid IgG clearance suggested a failure of the engrafted human lymphoid cells to maintain high circulating levels of human IgG. The higher levels of human CD4+ T cells and the normalization of the CD4:CD8 ratio that are observed in human PBMC-engrafted NOD/LtSz-scid/scid B2m(null) mice suggest that this system may be an excellent model for studies of HIV pathogenesis.
Fluidised bed pyrolysis and catalytic pyrolysis of scrap tyres (2003)

Pyrolysis of scrap tyres was undertaken in a semi-continuous fluidised bed reactor in relation to the temperature of the fluidised bed. Subsequently, a fixed bed of Zeolite catalyst was placed in the freeboard of the reactor. The catalyst temperature was held constant at 500 degrees C and the influence of the temperature of the fluidised bed over the same temperature range as the uncatalysed pyrolysis examined. Two Zeolite catalysts were examined, a Y-type Zeolite catalyst and Zeolite ZSM-5 catalyst of differing pore size and surface activity. The main aim of the work was to examine the production of certain single ring aromatic compounds in the derived pyrolysis oil which are known to be of commercial value. The oils were therefore analysed in detail to determine the concentration of benzene, toluene, xylenes and limonene. In addition, detailed analyses of the derived gases under pyrolysis and catalytic pyrolysis conditions were determined. The influence of the temperature of pyrolysis was to increase the yield of benzene, toluene and xylenes but decrease the yield of limonene. In the presence of the catalyst, the yield of oil was reduced with a consequent increase in the gas yield. Benzene, toluene and xylenes present in the oils showed a significant increase in the presence of both of the catalysts. The two catalysts used, although of differing surface acidities and selective pore sizes, produced similar concentrations of benzene, toluene, xylene and limonene.
Dual window method for processing spectroscopic optical coherence tomography signals with high spectral and spatial resolution (2009)

The generation of spectroscopic optical coherence tomography (SOCT) signals suffers from an inherent trade off between spatial and spectral resolution. Here, we present a dual window (DW) method that uses two Gaussian windows to simultaneously obtain high spectral and spatial resolution. We show that the DW method probes the Winger time-frequency distribution (TFD) with two orthogonal windows set by the standard deviation of the Gaussian windows used for processing. We also show that in the limit of an infinitesimally narrow window, combined with a large window, this method is equivalent to the Kirkwood &amp; Richaczek TFD and, if the real part is taken, it is equivalent to the Margenau &amp; Hill (MH) TFD. We demonstrate the effectiveness of the method by simulating a signal with four components separated in depth or center frequency. Six TFD are compared: the ideal, the Wigner, the MH, narrow window short time Fourier transform (STFT), wide window STFT, and the DW. The results show that the DW method contains features of the Wigner TFD, and that it contains the highest spatial and spectral resolution that is free of artifacts. This method can enable powerful applications, including accurate acquisition of the spectral information for cancer diagnosis.
Differential expression of hepatic sterol carrier proteins in the streptozotocin-treated diabetic rat. (1995)

Sterol carrier protein-2 (SCP2) is a 13.2-kilodalton protein that has been implicated in intracellular cholesterol transport, whereas a related sterol carrier protein, sterol carrier protein-X (SCPx; 58 kilodaltons) has been suggested to function also in the beta-oxidation of fatty acids. Although diabetes-related hyperlipidemia and altered cholesterol metabolism have been extensively studied, the intracellular cholesterol transport capacity during hyperglycemic states has not been examined. The fact that beta-oxidation is increased in diabetes whereas hepatic cholesterol metabolism is reduced suggests that differential expression of these sterol carrier proteins may accompany diabetic dyslipidemia. In this study, SCP2 protein levels were reduced by 60% in mildly hypercholesterolemic (cholesterol, > 130 and < 150 mg/dl; P < 0.01) diabetic rats and by 90% in severely hypercholesterolemic (cholesterol, > 150 mg/dl; P < 0.002) diabetic animals. In contrast, hepatic SCPx protein expression increased (3.5-fold) after diabetes induction with streptozotocin (STZ). The decline in SCP2 was inversely related to serum cholesterol levels. Hepatic SCP messenger RNA levels examined by ribonuclease protection assay demonstrated that hepatic SCP messenger RNA was increased 2-fold in diabetic animals. Northern blot analysis indicated that both the 0.8-kilobase SCP2-specific and the 2.1-kilobase SCPx-specific transcripts increased after STZ injection. SCPx protein induction preceded the decline in SCP2 by 4-5 days. Insulin treatment reversed the increase in SCPx and prevented the decline in SCP2. We conclude that SCP2 and SCPx are differentially expressed in the STZ-diabetic rat and suggest that this change in SCP expression should be considered a potential contributing mechanism through which cholesterol metabolism may be altered in diabetes.