gebhart/patrepeval huggingface dataset:
Synergistically Integrated Nanoparticles as Multimodal Probes for Nanobiotechnology (2008)

Current biomedical imaging techniques including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed X-ray tomography (CT) are vital in the diagnosis of various diseases. Each imaging modality has its own merits and disadvantages, and a single technique does not possess all the required capabilities for comprehensive imaging. Therefore, multimodal imaging methods are quickly becoming important tools for state-of-the-art biomedical research and clinical diagnostics and therapeutics. In this Account, we will discuss synergistically integrated nanoparticle probes, which will be an essential tool in multimodal imaging technology. When inorganic nanoparticles are introduced into biological systems, their extremely small size and their exceptional physical and chemical properties make them useful probes for biological diagnostics. Nanoparticle probes can endow imaging techniques with enhanced signal sensitivity, better spatial resolution, and the ability to relay information about biological systems at the molecular and cellular levels. Simple magnetic nanoparticles function as MRI contrast enhancement probes. These magnetic nanoparticles can then serve as a core platform for the addition of other functional moieties including fluorescence tags, radionuclides, and other biomolecules for multimodal imaging, gene delivery, and cellular trafficking. For example, MRI-optical dual-modal probes composed of a fluorescent dye-doped silica (DySiO(2)) core surrounded by magnetic nanoparticles can macroscopically detect neuroblastoma cancer cells via MRI along with subcellular information via fluorescence imaging. Magnetic nanoparticles can also be coupled to radionuclides ((124)I) to construct MRI-PET dual-modal probes. Such probes can accurately detect lymph nodes (LNs), which are critical for assessing cancer metastasis. In vivo MRI/PET images can clearly identify small (approximately 3 mm) LNs along with precise anatomical information. Systems using multicomponent nanoparticles modified with biomolecules can also monitor gene expression and other markers in cell therapeutics studies. We have used hybrid stem cell-magnetic nanoparticle probes with MRI to monitor in vivo stem cell trafficking. MRI with hybrid probes of magnetic nanoparticles and adenovirus can detect target cells and can monitor gene delivery and the expression of green fluorescent proteins optically. Each component of such multimodal probes complements the other modalities, and their synergistic materials properties ultimately provide more accurate information in in vitro and in vivo biological systems.
Improved large-MIMO detection based on damped belief propagation (2010)

In this paper, we consider the application of belief propagation (BP) to achieve near-optimal signal detection in large multiple-input multiple-output (MIMO) systems at low complexities. Large-MIMO architectures based on spatial multiplexing (V-BLAST) as well as non-orthogonal space-time block codes(STBC) from cyclic division algebra (CDA) are considered. We adopt graphical models based on Markov random fields (MRF) and factor graphs (FG). In the MRF based approach, we use pairwise compatibility functions although the graphical models of MIMO systems are fully/densely connected. In the FG approach, we employ a Gaussian approximation (GA) of the multi-antenna interference, which significantly reduces the complexity while achieving very good performance for large dimensions. We show that i) both MRF and FG based BP approaches exhibit large-system behavior, where increasingly closer to optimal performance is achieved with increasing number of dimensions, and ii) damping of messages/beliefs significantly improves the bit error performance.
α‐Synuclein contributes to GSK‐3β‐catalyzed Tau phosphorylation in Parkinson's disease models (2009)

We have shown in the parkinsonism-inducing neurotoxin MPP(+)/MPTP model that alpha-Synuclein (alpha-Syn), a presynaptic protein causal in Parkinson's disease (PD), contributes to hyperphosphorylation of Tau (p-Tau), a protein normally linked to tauopathies, such as Alzheimer's disease (AD). Here, we investigated the kinase involved and show that the Tau-specific kinase, glycogen synthase kinase 3beta (GSK-3beta), is robustly activated in various MPP(+)/MPTP models of Parkinsonism (SH-SY5Y cotransfected cells, mesencephalic neurons, transgenic mice overexpressing alpha-Syn, and postmortem striatum of PD patients). The activation of GSK-3beta was absolutely dependent on the presence of alpha-Syn, as indexed by the absence of p-GSK-3beta in cells lacking alpha-Syn and in alpha-Syn KO mice. MPP(+) treatment induced translocation and accumulation of p-GSK-3beta in nuclei of SH-SY5Y cells and mesencephalic neurons. Through coimmunoprecipitation (co-IP), we found that alpha-Syn, pSer396/404-Tau, and p-GSK-3beta exist as a heterotrimeric complex in SH-SY5Y cells. GSK-3beta inhibitors (lithium and TDZD-8) protected against MPP(+)-induced events in SH-SY5Y cells, preventing cell death and p-GSK-3beta formation, by reversing increases in alpha-Syn accumulation and p-Tau formation. These data unveil a previously unappreciated role of alpha-Syn in the induction of p-GSK-3beta, and demonstrate the importance of this kinase in the genesis and maintenance of neurodegenerative changes associated with PD.
Mutaphrase (2007)

We describe a preliminary version of Mutaphrase, a system that generates paraphrases of semantically labeled input sentences using the semantics and syntax encoded in FrameNet, a freely available lexicosemantic database. The algorithm generates a large number of paraphrases with a wide range of syntactic and semantic distances from the input. For example, given the input "I like eating cheese", the system outputs the syntactically distant "Eating cheese is liked by me", the semantically distant "I fear sipping juice", and thousands of other sentences. The wide range of generated paraphrases makes the algorithm ideal for a range of statistical machine learning problems such as machine translation and language modeling as well as other semanticsdependent tasks such as query and language generation.
Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest (2014)

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.
Simple poly(pyridine)ruthenium(II) photosensitizer: (2,2'-bipyridine)tetracyanoruthenate(II) (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimple poly(pyridine)ruthenium(II) photosensitizer: (2,2'-bipyridine)tetracyanoruthenate(II)C. A. Bignozzi, C. Chiorboli, M. T. Indelli, M. A. Rampi Scandola, G. Varani, and F. ScandolaCite this: J. Am. Chem. Soc. 1986, 108, 24, 7872–7873Publication Date (Print):November 1, 1986Publication History Published online1 May 2002Published inissue 1 November 1986https://pubs.acs.org/doi/10.1021/ja00284a084https://doi.org/10.1021/ja00284a084research-articleACS PublicationsRequest reuse permissionsArticle Views750Altmetric-Citations107LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Molecular determinants of intrinsic resistance to doxorubicin in human cancer cell lines (2003)

Intrinsic or acquired drug resistance poses a major challenge to the success of chemotherapy in the clinical management of human cancers. While acquired multidrug resistance (MDR), whereby cells become refractory to multiple drugs, has been extensively investigated, the mechanistic basis for intrinsic resistance remains elusive, so that this condition is largely unmanageable in the clinical setting. To address this issue, we have assessed the effects of the anticancer agent doxorubicin (DX) on a panel of human tumor cell lines originally derived from untreated patients and tried to establish a correlation between cell response and a number of parameters, including drug accumulation and/or drug efflux; differences in expression and/or subcellular distribution of proteins involved in the apoptotic process (e.g., p53, Bcl-2, Bax) and intracellular signal transducers (PKCalpha); changes in key detoxification processes. Based on our results, 'classic' multispecific drug transporters (P-glycoprotein, MDR-related proteins) only seem to play a minor role in the intrinsically resistant phenotype, whereas LRP may contribute to resistance in non-small cell lung carcinoma (NSCLC) cells. No relationship was observed between drug response and expression and/or subcellular localization of apoptosis-related proteins; however, increased PKCalpha levels are associated with poor drug response, suggesting that one or more substrates of this enzyme may be relevant to the resistant phenotype. Finally, overactive glutathione-recycling pathways may contribute to DX resistance.
Bromodomain and extraterminal domain inhibition synergizes with WEE1‐inhibitor AZD1775 effect by impairing nonhomologous end joining and enhancing DNA damage in nonsmall cell lung cancer (2019)

Bromodomain and extraterminal domain (BET) inhibitors are broadly active against distinct types of cancer, including nonsmall cell lung cancer (NSCLC). Previous studies have addressed the effect of BET-inhibiting drugs on the expression of oncogenes such as c-Myc, but DNA damage repair pathways have also been reported to be involved in the efficacy of these drugs. AZD1775, an inhibitor of the G2-M cell cycle checkpoint kinase WEE1, induces DNA damage by promoting premature mitotic entry. Thus, we hypothesized that BET inhibition would increase AZD1775-induced cytotoxicity by impairing DNA damage repair. Here, we demonstrate that combined inhibition of BET and WEE1 synergistically suppresses NSCLC growth both in vitro and in vivo. Two BET inhibitors, JQ1 and AZD5153, increased and prolonged AZD1775-induced DNA double-strand breaks (DSBs) and concomitantly repressed genes related to nonhomologous end joining (NHEJ), including XRCC4 and SHLD1. Furthermore, pharmaceutical inhibition of BET or knockdown of the BET protein BRD4 markedly diminished NHEJ activity, and the BET-inhibitor treatment also repressed myelin transcription factor 1 (MYT1) expression and promoted mitotic entry with subsequent mitotic catastrophe when combined with WEE1 inhibition. Our findings reveal that BET proteins, predominantly BRD4, play an essential role in DSB repair through the NHEJ pathway, and further suggest that combined inhibition of BET and WEE1 could serve as a novel therapeutic strategy for NSCLC.
Murine induced pluripotent stem cells can be derived from and differentiate into natural killer T cells (2010)

NKT cells demonstrate antitumor activity when activated to produce Th1 cytokines by DCs loaded with alpha-galactosylceramide, the prototypic NKT cell-activating glycolipid antigen. However, most patients do not have sufficient numbers of NKT cells to induce an effective immune response in this context, indicating a need for a source of NKT cells that could be used to supplement the endogenous cell population. Induced pluripotent stem cells (iPSCs) hold tremendous potential for cell-replacement therapy, but whether it is possible to generate functionally competent NKT cells from iPSCs has not been rigorously assessed. In this study, we successfully derived iPSCs both from embryonic fibroblasts from mice harboring functional NKT cell-specific rearranged T cell receptor loci in the germline and from splenic NKT cells from WT adult mice. These iPSCs could be differentiated into NKT cells in vitro and secreted large amounts of the Th1 cytokine IFN-gamma. Importantly, iPSC-derived NKT cells recapitulated the known adjuvant effects of natural NKT cells and suppressed tumor growth in vivo. These studies demonstrate the feasibility of expanding functionally competent NKT cells via an iPSC phase, an approach that may be adapted for NKT cell-targeted therapy in humans.
Pharmacologic Interventions for the Treatment of Opioid Dependence and Withdrawal (1990)

This article discusses current pharmacologic methods in the treatment of heroin dependence and withdrawal. Methadone hydrochloride, the most commonly used opiate agonist, is used for both withdrawal and maintenance therapy. However, it produces dependence and withdrawal results upon abrupt discontinuation. Other opiate agonists including L-alpha acetyl methadyl (LAAM) and propoxyphene napsylate have been used for both withdrawal and maintenance therapy. LAAM is currently available only as an investigational agent and propoxyphene is easily accessible but has been associated with hallucinations and dysphoria at high doses. Alpha 2-adrenergic agonists decrease opiate withdrawal symptoms by decreasing the central adrenergic hyperarousal that is associated with withdrawal. Clonidine effectively attenuates but does not totally eliminate withdrawal symptoms. Other alpha 2-adrenergic agonists (e.g., lofexidine hydrochloride, guanfacine hydrochloride, and guanabenz) have undergone only preliminary investigations. Although alpha 2 agonists effectively decrease most withdrawal symptoms they often cause hypotension. Buprenorphine hydrochloride is a partial opiate agonist that shows some promise in the treatment of the heroin-dependent population. It attenuates opiate craving and causes only minimal withdrawal upon abrupt discontinuation. Because it is well accepted by the heroin-dependent population, however, it may ultimately become an abused substance. Naltrexone is a potent, orally acting opiate antagonist that blocks all opiate-agonist effects and causes no euphoria. Unfortunately, it has not been well accepted by the heroin-dependent population. Scant research has been conducted concerning the use of adjunctive medications during opioid withdrawal.
Cloning and expression of the two genes coding for L-serine dehydratase from Peptostreptococcus asaccharolyticus: relationship of the iron-sulfur protein to both L-serine dehydratases from Escherichia coli (1997)

The structural genes sdhA and sdhB, coding for the alpha- and beta-subunits of the [4Fe-4S] cluster containing L-serine dehydratase from Peptostreptococcus asaccharolyticus, have been cloned and sequenced. Expression of modified sdhB together with sdhA in Escherichia coli led to overproduction of active His6-tagged L-serine dehydratase. E. coli MEW22, deficient in the L-serine dehydratase L-SD1, was complemented by this sdhBA construct. The derived amino acid sequence of SdhBA shares similarities with both monomeric L-serine dehydratases, L-SD1 and L-SD2, from E. coli and with a putative L-serine dehydratase from Haemophilus influenzae, which suggests that these three enzymes are also iron-sulfur proteins.
Automated summarization of narrative video on a semantic level (2007)

The movie industry produces thousands of feature films and TV series annually. Such massive data volumes would take consumers more than a lifetime to watch. Therefore, summarization of narrative media, which engages in providing concise and informative video summaries, has become a popular topic of research. However, most of the summarization solutions so far aim to represent just the overall atmosphere of the video at the expense of the story line. In this paper we describe a novel approach for automated creation of summaries for narrative videos. We propose an automated content analysis and summarization framework for creating moving-image summaries. We aim at preserving the story line to the level that users can watch the summary instead of the original content. Our solution is based on textual cues available in subtitles and movie scripts. We extract features like keywords, main characters names and presence, and combine them in an importance function to identify the moments most relevant for preserving the story line. We develop several summarization methods and evaluate the quality of the resulting summaries in terms of user understanding and user satisfaction through a user test.
Pharmacological Enhancement of β-Hexosaminidase Activity in Fibroblasts from Adult Tay-Sachs and Sandhoff Patients (2004)

Tay-Sachs and Sandhoff diseases are lysosomal storage disorders that result from an inherited deficiency of beta-hexosaminidase A (alphabeta). Whereas the acute forms are associated with a total absence of hexosaminidase A and early death, the chronic adult forms exist with activity and protein levels of approximately 5%, and unaffected individuals have been found with only 10% of normal levels. Surprisingly, almost all disease-associated missense mutations do not affect the active site of the enzyme but, rather, inhibit its ability to obtain and/or retain its native fold in the endoplasmic reticulum, resulting in its retention and accelerated degradation. By growing adult Tay-Sachs fibroblasts in culture medium containing known inhibitors of hexosaminidase we have raised the residual protein and activity levels of intralysosomal hexosaminidase A well above the critical 10% of normal levels. A similar effect was observed in fibroblasts from an adult Sandhoff patient. We propose that these hexosaminidase inhibitors function as pharmacological chaperones, enhancing the stability of the native conformation of the enzyme, increasing the amount of hexosaminidase A capable of exiting the endoplasmic reticulum for transport to the lysosome. Therefore, pharmacological chaperones could provide a novel approach to the treatment of adult Tay-Sachs and possibly Sandhoff diseases.
Controlled Production of Emulsions Using a Crossflow Membrane (1998)

A method for manufacturing emulsions — crossflow membrane emulsification has been studied. This involves the formation of emulsions by breaking up the discontinuous phase into droplets in a controlled manner without the use of turbulent eddies. This is achieved by passing the discontinuous phase through a suitable microporous medium and injecting the droplets so formed directly into a moving continuous phase. This paper presents two examples of experimental data for droplet formation using a single pore (capillary tube) and a membrane tube. A high-speed video camera (up to 1000 frames per second) was used to record the formation of droplet from a single pore and thus measure droplet growth and the detachment processes as a function of process parameters such as transmembrane pressure drop, membrane pore size, continuous phase crossflow velocity etc. Real emulsions were prepared using a membrane tube.
Determination of Anabolic Agents in Beef by High Performance Liquid Chromatography (1989)

A high performance liquid chromatographic procedure with ultraviolet detection was developed for determination of 15 anabolic agents in beef. The following agents were studied. Estrogens: zeranol, 17α-estradiol, 17β-estradiol, dienestrol, diethylstilbestrol, hexestrol, 17α-ethynylestradiol; ketosteroids: 19-nortestosterone, testosterone, progesterone, 17α-methyltestosterone, medroxyprogesterone; esters: 17β-estradiol 3-benzoate, medroxy progesterone acetate, melengestrol acetate.These agents were extracted with acetonitrile from beef and reextracted into dichloromethane. The concentrated crude extract was purified by liquid-liquid partition between hexane and 90% methanol, and then fractionated into two parts (ketosteroids and esters fraction and estrogens fraction) by chromatography on Bond Elut DEA. Each fraction was further purified on an LH20 column and subjected to high performance liquid chromatography. Ketosteroids and esters were determined on a LiChrospher RP-18 (4×250mm) column with McCN: H2O=65:35 as the mobile phase at 240nm and at 290nm for melengestrol acetate, and estrogens were determined on the same column with McCN: H2O=50:65 at 230nm. Fifteen anabolic agents in beef at levels as low as ca. 10ppb were determined by the proposed method. The mean recoveries of these compounds added to beef at 20ppb were 78.4-100.8%.
Optical Time-of-Flight and Absorbance Imaging of Biologic Media (1993)

Imaging the interior of living bodies with light may assist in the diagnosis and treatment of a number of clinical problems, which include the early detection of tumors and hypoxic cerebral injury. An existing picosecond time-of-flight and absorbance (TOFA) optical system has been used to image a model biologic system and a rat. Model measurements confirmed TOFA principles in systems with a high degree of photon scattering; rat images, which were constructed from the variable time delays experienced by a fixed fraction of early-arriving transmitted photons, revealed identifiable internal structure. A combination of light-based quantitative measurement and TOFA localization may have applications in continuous, noninvasive monitoring for structural imaging and spatial chemometric analysis in humans.