gebhart/patrepeval huggingface dataset:
Slow-Onset, Long-Duration 3-(3‘,4‘-Dichlorophenyl)-1-indanamine Monoamine Reuptake Blockers as Potential Medications To Treat Cocaine Abuse (2000)

A series of 3-(3',4'-dichlorophenyl)-1-indanamine monoamine reuptake blockers have been synthesized in an effort to develop a compound that could be used as a maintenance therapy to treat cocaine abuse. Since the effects of cocaine on dopamine (DA) and serotonin (5HT) transporters are important components of its pharmacological activity, the focus was on nonselective inhibitors of monoamine transport. To reduce or eliminate the abuse potential of a DA reuptake blocker, the compounds were designed to be slow-onset, long-duration prodrugs whose N-demethylated metabolites would have increased activity over the parent compound with the ideal being a parent compound that has little or no activity. To achieve this, pairs of compounds with different groups on the amine nitrogen and with and without an additional N-methyl group were synthesized. All of the synthesized compounds were screened for binding and reuptake at the cloned human DA, 5HT, and norepinephrine (NE) transporters. As previously found, trans isomers are nonselective blockers of DA, 5HT, and NE reuptake, cis isomers with small N-alkyl groups are selective blockers of 5HT reuptake, and tertiary amines of the trans compounds are less potent than the corresponding N-demethylated secondary amines as blockers of DA reuptake. Larger N-alkyl groups in both the trans and cis series were found to reduce activity for the 5HT and NE transporters with less effect at DA transporters. Selected trans compounds were also screened for locomotor activity in mice and generalization to a cocaine-like profile in rats. With intraperitoneal administration, all of the trans isomers showed a slow onset of at least 20 min and an extremely long duration of action in the locomotor assays. Several of the trans compounds also fully generalized to a cocaine-like pharmacological profile. An initial lead compound, the N,N-dimethyl analogue trans-1b, was resolved into chirally pure enantiomers. Surprisingly, both enantiomers were found to have significant affinity for the DA transporter and to cause locomotor activation. This is in contrast to the N-methyl compound in which only the (+)-enantiomer had significant activity. The absolute configuration of the more active enantiomer was determined by X-ray crystallography to be 3R,1S.
Detecting expression of 5T4 in CTCs and tumor samples from NSCLC patients (2017)

The fetal oncogene 5T4 is a cell surface protein, with overexpression observed in a variety of cancers as compared to normal adult tissue. The ability to select patients with tumors that express high levels of 5T4 may enrich a clinical trial cohort with patients most likely to respond to 5T4 targeted therapy. To that end, we developed assays to measure 5T4 in both tumors and in circulating tumor cells (CTCs). We identified the presence of 5T4 in both adenocarcinoma and squamous cell carcinoma of lung, in all clinical stages and grades of disease. CTCs were identified in peripheral blood from the majority of patients with NSCLC, and 5T4 was detectable in most samples. Although 5T4 was present in both CTCs and tumors in most patients, there was no concordance between relative amount in either sample type. Clinical response rates of patients treated with the therapies directed against 5T4 in early stage clinical trials, as determined by these assays, may provide important insights into the biology of 5T4 in tumors and the mechanisms of action of 5T4-targeting therapy.
A FRET-Based Approach to Ratiometric Fluorescence Detection of Hydrogen Peroxide (2006)

We report the synthesis, properties, and biological applications of Ratio-Peroxyfluor-1 (RPF1), a new ratiometric fluorescent reporter for hydrogen peroxide. RPF1 is comprised of a two-fluorophore cassette, where the spectral overlap between coumarin donor and fluoran/fluorescein acceptor partners can be controlled by the chemoselective peroxide-mediated deprotection of boronic ester pendants on the acceptor dye. RPF1 features good selectivity for hydrogen peroxide over a variety of reactive oxygen species, including superoxide and nitric oxide, a ca. 8-fold increase in fluorescence intensity ratio (lambda517/lambda464) upon H2O2 reaction, and excitation and emission profiles in the visible region. Experiments with viable yeast mitochondria show that RPF1 can monitor and quantify endogenous production of H2O2, establishing the potential utility of this approach for probing peroxide biology in living systems.
Abstract 2394: The role of DNA repair in breast cancer risk and recurrence (2014)

Abstract BACKGROUND: Breast cancer (BC) is a complex disease that is caused by multiple factors. Deficits in DNA repair capacity (DRC) are known to cause certain familial BC, and dysregulation of DRC develops with progressive carcinogenesis. However, the effect of DRC on carcinogenesis of sporadic breast tumors has not been well characterized_and the factors associated with DRC variability are still poorly understood. DNA repair is integral to maintain genomic integrity, and carcinogenesis occurs when efficient, effective DNA repair is impaired. Our laboratory has just finished the recruitment of nearly 1,200 women in a seven-year molecular epidemiology study focused on the role of DRC as a risk factor for BC. OBJECTIVE: Our aim is to present key findings on the role of DRC as a risk factor for BC and its potential association with BC recurrence. METHODS: A personal interview was conducted for soliciting information on BC risk factors. Among the 493 BC cases and 683 controls the DRC was measured in lymphocytes using a host cell reactivation assay with a luciferase reporter gene. We stratified the women with BC using the median of the DRC level and selected 70 women with a low DRC level (&lt;2.8%) who had been enrolled in the study for at least 5 years in order to assess the BC recurrence. RESULTS: Our 7 year study of DRC of female cohorts in Puerto Rico has shown that women with BC have a DRC that, on average, is 51% lower than women without BC (P &lt; 0.001, Mann Whitney U-test). Women with low DRC have 6.8 (95%CI 5.2, 9.0) times the odds for BC when compared with women with high DRC level. So far, the overall BC recurrence was 17% and the 5-year mortality was 10%. Recurrence was primarily in the lung, liver, bone, or occurred as generalized metastatic disease. CONCLUSIONS: Using a large sample size (n=1,183 participants), we show that women with BC had on an average a 51% lower DRC than controls (P&lt;0.001). We also present the first data on the potential between a low DRC and risk of BC recurrence. With a larger sample size, we will test the hypothesis that low DRC can predict risk of BC recurrence. Supported by grants from the NCI Center to Reduce Health Disparities through the NIH-MBRS Program grants S06 GM008239-20, 9SC1CA182846-04 to PSMHS through JM and MBRS-RISE GM082406 through CO. Citation Format: Jaime L. Matta, Erick Suarez, Wanda Vargas, Carmen Ortiz, Manuel Bayona, Luisa Morales. The role of DNA repair in breast cancer risk and recurrence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2394. doi:10.1158/1538-7445.AM2014-2394
Spatial and spectral detection of protein monolayers with deterministic aperiodic arrays of metal nanoparticles (2010)

Light scattering phenomena in periodic systems have been investigated for decades in optics and photonics. Their classical description relies on Bragg scattering, which gives rise to constructive interference at specific wavelengths along well defined propagation directions, depending on illumination conditions, structural periodicity, and the refractive index of the surrounding medium. In this paper, by engineering multifrequency colorimetric responses in deterministic aperiodic arrays of nanoparticles, we demonstrate significantly enhanced sensitivity to the presence of a single protein monolayer. These structures, which can be readily fabricated by conventional Electron Beam Lithography, sustain highly complex structural resonances that enable a unique optical sensing approach beyond the traditional Bragg scattering with periodic structures. By combining conventional dark-field scattering micro-spectroscopy and simple image correlation analysis, we experimentally demonstrate that deterministic aperiodic surfaces with engineered structural color are capable of detecting, in the visible spectral range, protein layers with thickness of a few tens of Angstroms.
Safe Reinforcement Learning with Scene Decomposition for Navigating\n Complex Urban Environments (2019)

Navigating urban environments represents a complex task for automated\nvehicles. They must reach their goal safely and efficiently while considering a\nmultitude of traffic participants. We propose a modular decision making\nalgorithm to autonomously navigate intersections, addressing challenges of\nexisting rule-based and reinforcement learning (RL) approaches. We first\npresent a safe RL algorithm relying on a model-checker to ensure safety\nguarantees. To make the decision strategy robust to perception errors and\nocclusions, we introduce a belief update technique using a learning based\napproach. Finally, we use a scene decomposition approach to scale our algorithm\nto environments with multiple traffic participants. We empirically demonstrate\nthat our algorithm outperforms rule-based methods and reinforcement learning\ntechniques on a complex intersection scenario.\n
Micelles for Delivery of Nitric Oxide (2009)

We designed block copolymer pro-amphiphiles and amphiphiles for providing very long-term release of nitric oxide (NO). A block copolymer of N-acryloylmorpholine (AM, as a hydrophile) and N-acryloyl-2,5-dimethylpiperazine (AZd, as a hydrophilic precursor) was synthesized. The poly(N-acryloyl-2,5-dimethylpiperazine) (PAZd) is water-soluble, but chemical reaction of the secondary amines with NO to form a N-diazeniumdiolate (NONOate) converts the hydrophilic PAZd into a hydrophobic poly(sodium-1-(N-acryloyl-2,5-dimethylpiperazin-1-yl)diazen-1-ium-1,2-diolate) (PAZd.NONOate), driving aggregation. The PAM block guides this process toward micellization, rather than precipitation, yielding ca. 50 nm spherical micelles. The hydrophobic core of the micelle shielded the NONOate from the presence of water, and thus protons, which are required for NO liberation, delaying release to a remarkable 7 d half-life. Release of the NO returned the original soluble polymer. The very small NO-loaded micelles were able to penetrate complex tissue structures, such as the arterial media, opening up a number of tissue targets to NO-based therapy.
Isolation of a new dual‐functional caffeine synthase gene encoding an enzyme for the conversion of 7‐methylxanthine to caffeine from coffee (<i>Coffea arabica</i> L.)<sup>1</sup> (2002)

In coffee and tea plants, caffeine is synthesized from xanthosine via a pathway that includes three methylation steps. We report the isolation of a bifunctional coffee caffeine synthase (CCS1) clone from coffee endosperm by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) technique using previously reported sequence information for theobromine synthases (CTSs). The predicted amino acid sequences of CCS1 are more than 80% identical to CTSs and are about 40% similar to those of tea caffeine synthase (TCS1). Interestingly, CCS1 has dual methylation activity like tea TCS1.
Surface-Coverage Dependence of Surface-Enhanced Raman Scattering from Gold Nanocubes on Self-Assembled Monolayers of Analyte (2009)

Surface enhanced Raman scattering (SERS) spectra of 4-mercaptobenzoic acid (4-MBA) self-assembled monolayers (SAMs) on gold substrates are presented for SAMs onto which gold nanocubes have been electrostaticaly immobilized. In the absence of nanocubes, no SERS signals from 4-MBA SAMs are observed. Upon addition of the gold nanocubes to the SAM, a sandwich architecture is formed, allowing for coupling between the localized surface plasmon of the nanocubes and the surface plasmon of the gold substrate. This creates a large electromagnetic field in the area where the 4-MBA molecules reside, causing the characteristic vibrational modes of 4-MBA to appear. SERS intensities increase linearly with increasing nanocube coverage up to a factor of 7 in the best case studied here, with enhancement factors of up to 10(13).
A rapid screening method to detect nonsense and frameshift mutations: identification of disease-causing APC alleles. (1993)

A functional screen for nonsense and frameshift mutations has been devised that allows genes of interest to be scanned in segments. This assay is based on the cloning of these segments in-frame with a colorimetric marker gene (lacZ) followed by screening for the level of functional activity from the marker polypeptide (beta-galactosidase). Individuals at risk for any one of a number of genetic diseases, in particular familial adenomatous polyposis coli (APC), can be quickly screened for chain-terminating mutations introduced by stops and frameshifts. At present, scanning of the APC gene for mutation requires significant effort because it is a large gene and most APC mutations are unique. Therefore, this assay offers a powerful option for the diagnosis of this and other genetic diseases, as well as great potential for the development of a similar rapid screen to detect APC mutations in colorectal adenomas and carcinomas.
Inhibition of cartilage degeneration and subchondral bone deterioration by <i>Spinacia oleracea</i> in human mimic of ACLT-induced osteoarthritis (2020)

Osteoarthritis (OA) is an aging disorder characterized by degenerated cartilage and sub-chondral bone alteration in affected knee joints. Globally, millions of people suffer from this disease. However, there is a lack of safe and promising therapeutics, making the exploration and development of leads from natural sources urgent. Accordingly, food as medicine may be the most suitable approach for the treatment of this degenerative disease. Herein, we elucidated the protective role of Spinacia oleracea extract (SOE) in an anterior cruciate ligament transection (ACLT) model of osteoarthritis as a mimic of the human condition. ACL transection was done in the tibio-femoral joints of rats. SOE was orally administered at the dosage of 125 and 250 mg kg-1 day-1 for four weeks. It was shown that the animals with SOE treatment had better joint morphology than the ACLT animals, as evident by the shiny appearance of their cartilage. Hematoxylin and safranin-o staining showed that the number of chondrocytes was significantly reduced in the OA model, which was prevented with SOE treatment. The reduction in the cartilage thickness was well observed by toluidine blue staining. The reduced stain by safranin-o and toluidine blue, indicated proteoglycan loss in the ACLT-induced osteoarthritis model. The proteoglycan content and cartilage thickness were restored in the SOE group upon treatment at an SOE dosage of 125 and 250 mg kg-1 day-1. The micro-CT parameters of subchondral bone (SCB) and cartilage degradation markers in the serum corroborated our findings of the protective effects of SOE. In summary, our study suggests that SOE has therapeutic potential, which if taken regularly as a food supplement, can have beneficial effects.
Nanoscale ablation with soft x-ray lasers (2007)

We have demonstrated ablation of holes with diameter as small as 82 nm in polymethyl methacrylate (PMMA) by focusing the output of a capillary discharge soft x-ay laser with a Fresnel zone plate. We also report the first demonstration of laser induced breakdown spectroscopy with soft x-ray laser light.
Concatenated Multitype L2 Fusion Proteins as Candidate Prophylactic Pan-Human Papillomavirus Vaccines (2009)

Concatenated multitype L2 proteins in adjuvant have potential as pan-oncogenic HPV vaccines.
A Flexible Spatio-Temporal Indexing Scheme for Large-Scale GPS Track Retrieval (2008)

The increasing popularity of GPS device has boosted many Web applications where people can upload, browse and exchange their GPS tracks. In these applications, spatial or temporal search function could provide an effective way for users to retrieve specific GPS tracks they are interested in. However, existing spatial-temporal index for trajectory data has not exploited the characteristic of user behavior in these online GPS track sharing applications. In most cases, when sharing a GPS track, people are more likely to upload GPS data of the near past than the distant past. Thus, the interval between the end time of a GPS track and the time it is uploaded, if viewed as a random variable, has a skewed distribution. In this paper, we first propose a probabilistic model to simulate user behavior of uploading GPS tracks onto an online sharing application. Then we propose a flexible spatio-temporal index scheme, referred to as Compressed Start-End Tree (CSE-tree), for large-scale GPS track retrieval. The CSE-tree combines the advantages of B+ Tree and dynamic array, and maintains different index structure for data with different update frequency. Experiments using synthetic data show that CSE-tree outperforms other schemes in requiring less index size and less update cost while keeping satisfactory retrieval performance.
An RFID-based object localisation framework (2011)

Numerous ubiquitous computing applications depend on the ability to locate objects as a key functionality. We show that Radio Frequency Identification (RFID) technology can be leveraged to achieve object localisation in an inexpensive, reliable, flexible, and scalable manner. We outline the challenges that can adversely affect RFID-based localisation techniques, and propose practical mitigating solutions. We present several new algorithms for RFID-based object localisation that compare favourably with previous methods in terms of accuracy, speed, reliability, scalability, and cost.
Improved Electrochromic Behavior of Reactively Sputtered Iridium Oxide Films (1981)

We report deposition parameters for improved electrochromic behavior of reactively sputtered iridium oxide films (SIROF's). When operated in electrolyte, SIROF's deposited under these conditions may be bleached to a state exhibiting, to within experimental error (<0.4%), zero transmission loss in the visible. SIROF's which can be fully colored to an optical density (OD) of 0.45 (single pass), show a response time for coloring or bleaching (through a ΔOD of 0.3) of 40 msec under constant voltage address. This may be reduced to 20 msec in each direction if IR compensation is employed. Preliminary data show no difference in color/bleach cycle lifetime from that of SIROF's deposited under slightly different conditions. No change in contrast is perceivable after cycles at room temperature.
Transgenic Tomato Plants that Overexpress a Gene for NADH-dependent Glutamate Dehydrogenase (legdh1) (2007)

Tomato plants were transformed with a plasmid that included a legdh1 gene for NADH-dependent glutamate dehydrogenase (NADH-GDH) from Lycopersicon esculentum Mill. coupled, in the sense orientation, with the constitutively active 35S promoter from cauliflower mosaic virus. Three independent transformants were obtained. In these transgenic lines, high-level expression of legdh1 mRNA was detected in the leaves, and the NADH-GDH activity in the leaves of the transgenic plants was approximately twice that in the leaves of the non-transgenic plant. In the transgenic tomato fruits examined for six successive weeks after flowering, the levels of total free amino acids were higher (2.1- to 2.3-fold) than those in the controls. In particular, the level of glutamate was about twice that in the control fruits.
Differentiating Alternative Splice Variant Patterns of Human Telomerase Reverse Transcriptase in Thyroid Neoplasms (2008)

These differences in gene expression patterns of hTERT alternative splice variants may provide a useful adjunct to FNA diagnosis of suspicious thyroid tumors.
Packetization of JPEG2000 codestreams (2002)

We introduce techniques that improve the error resilience of JPEG2000 against packet losses. The presented methods operate on JPEG2000 codestreams and consider the properties of different codestream segments. Experiments indicate that error resilience of JPEG2000 codestreams against packet losses can be improved significantly using these techniques. The performance of the proposed methods compares favorably with existing algorithms.
Attempted immunisation of cats against feline infectious peritonitis using canine coronavirus (1988)

Specific pathogen free kittens were vaccinated with an unattenuated field isolate of canine coronavirus (CCV) either by aerosol or subcutaneously, and received boosting vaccinations four weeks later. Aerosolisation elicited a homologous virus-neutralising (VN) antibody response that increased steadily over a four-week period and levelled off one to two weeks after revaccination. The initial aerosolised dose produced an asymptomatic infection with excretion of CCV from the oropharynx up to eight days after vaccination; virus shedding was not detected, however, after the second inoculation. Cats vaccinated subcutaneously developed low VN antibody titres after the first CCV dose and experienced a strong anamnestic response after the second dose. Neutralising antibody titres then levelled off one to two weeks after revaccination at mean values somewhat lower than in cats vaccinated by aerosol. CCV was not isolated from the oropharynx after either subcutaneous dose. Four weeks after CCV boosting inoculations, vaccinated cats and sham-vaccinated control cats were divided into three subgroups and challenged by aerosol with the virulent UCD1 strain of feline infectious peritonitis virus (FIPV UCD1) at three different dosage levels. Five of six cats (including sham-vaccinated controls) given the lowest challenge dose showed no signs of disease, while all other cats developed lesions typical of feline infectious peritonitis (FIP). The five surviving cats developed FIP after subsequent challenge with a fivefold higher dose of FIPV. Thus heterotypic vaccination of cats with CCV did not provide effective protection against FIPV challenge.