gebhart/patrepeval huggingface dataset:
Parkin Facilitates the Elimination of Expanded Polyglutamine Proteins and Leads to Preservation of Proteasome Function (2003)

Parkin, the most commonly mutated gene in familial Parkinson's disease, encodes an E3 ubiquitin ligase. A number of candidate substrates have been identified for parkin ubiquitin ligase action including CDCrel-1, o-glycosylated alpha-synuclein, Pael-R, and synphilin-1. We now show that parkin promotes the ubiquitination and degradation of an expanded polyglutamine protein. Overexpression of parkin reduces aggregation and cytotoxicity of an expanded polyglutamine ataxin-3 fragment. Using a cellular proteasome indicator system based on a destabilized form of green fluorescent protein, we demonstrate that parkin reduces proteasome impairment and caspase-12 activation induced by an expanded polyglutamine protein. Parkin forms a complex with the expanded polyglutamine protein, heat shock protein 70 (Hsp70) and the proteasome, which may be important for the elimination of the expanded polyglutamine protein. Hsp70 enhances parkin binding and ubiquitination of expanded polyglutamine protein in vitro suggesting that Hsp70 may help to recruit misfolded proteins as substrates for parkin E3 ubiquitin ligase activity. We speculate that parkin may function to relieve endoplasmic reticulum stress by preserving proteasome activity in the presence of misfolded proteins. Loss of parkin function and the resulting proteasomal impairment may contribute to the accumulation of toxic aberrant proteins in neurodegenerative diseases including Parkinson's disease.
A Buried Polar Interaction Imparts Structural Uniqueness in a Designed Heterodimeric Coiled Coil (1995)

Buried polar residues are a common feature of natural proteins. ACID-p1 and BASE-p1 are two designed peptides that form a parallel, heterodimeric coiled coil with a fixed tertiary structure [O'Shea, E. K., Lumb, K. J., & Kim, P. S. (1993) Curr. Biol. 3, 658-667]. The interface between the ACID-p1 and BASE-p1 helices consists of hydrophobic Leu residues, with the exception of a single polar residue, Asn 14. In the crystal structure of the GCN4 leucine zipper coiled coil, an analogous Asn is hydrogen bonded to the corresponding Asn of the opposing helix, thereby forming a buried polar interaction in an otherwise hydrophobic interface between the helices [O'Shea, E. K., Klemm, J. D., Kim, P. S., & Alber, T. (1991) Science 254, 539-544]. This buried polar interaction in the ACID-p1/BASE-p1 heterodimer was removed by substituting Asn 14 with Leu. The Asn 14-->Leu variants are significantly more stable than the p1 peptides and preferentially form a heterotetramer instead of a heterodimer. Strikingly, the heterotetramer does not fold into a unique structure; in particular, the helices lack a unique orientation. Thus, the Asn 14 residue imparts specificity for formation of a two-stranded, parallel coiled coil at the expense of stability. The results suggest that, whereas nonspecific hydrophobic interactions contribute to protein stability, the requirement to satisfy the hydrogen bonding potential of buried polar residues in the generally hydrophobic environment of the protein interior can impart specificity (structural uniqueness) to protein folding and design.
Fire blight: the disease and its causative agent, Erwinia amylovora. (2000)

<title>Abstract</title> This book is the first multi-authored book on fire blight, the most devastating bacterial disease of apples and pears. It is divided into three sections. The first section is about the disease: its epidemiology, its worldwide distribution and its economic importance, the host range of the pathogen and how it migrates and survives in the fruit tissues. The second section is about the causal agent, <italic>Erwinia amylovora</italic>: its general characteristics as a member of the Enterobacteriaceae, but also the weapons it uses to cause disease: amylovoran, harpin, avirulence factors and siderophores. In the third section, the authors address the difficult problems of fire blight control. They look at chemical control, problems associated with streptomycin resistance, potential and limitations of traditional breeding and transgenic plants, and risk assessment strategies for the control of fire blight in orchards and in nurseries.
In Vivo Detection of Head and Neck Cancer Orthotopic Xenografts by Immunofluorescence (2006)

Fluorescent immunoguided neoplasm detection may be used as a diagnostic tool and to guide surgical therapy by providing real-time imaging information about the extent of disease or the presence of residual disease.
Using Scalable Video Coding For Dynamic Adaptive Streaming Over Http In Mobile Environments (2012)

Publication in the conference proceedings of EUSIPCO, Bucharest, Romania, 2012
Channel Estimation Schemes for IEEE 802.11p Standard (2013)

In vehicle-to-vehicle (V2V) communications, reliable channel estimation is critical for the system performance due to the extremely time-varying characteristic of V2V channels. In this article, we present a survey on the current channel estimation techniques for the IEEE 802.11p standard. According to deficiencies of the current schemes and considering characteristics of V2V channels, we propose a novel channel estimation scheme, which utilizes the data symbols to construct pilots as well as the correlation characteristics between channels within two adjacent symbols. Analysis and simulation results demonstrate that the proposed scheme outperforms currently widely-used schemes especially in high signal-to-noise ratio regime. At the end, some open issues for the future work conclude this article.
Recursive MUSIC: A framework for EEG and MEG source localization (1998)

The multiple signal classification (MUSIC) algorithm can be used to locate multiple asynchronous dipolar sources from electroencephalography (EEG) and magnetocncephalography (MEG) data. The algorithm scans a single-dipole model through a three-dimensional (3-D) head volume and computes projections onto an estimated signal subspace. To locate the sources, the user must search the head volume for multiple local peaks in the projection metric. This task is time consuming and subjective. Here, the authors describe an extension of this approach which they refer to as recursive MUSIC (R-MUSIC). This new procedure automatically extracts the locations of the sources through a recursive use of subspace projections. The new method is also able to locate synchronous sources through the use of a spatio-temporal independent topographies (IT) model. This model defines a source as one or more nonrotating dipoles with a single time course. Within this framework, the authors are able to locate fixed, rotating, and synchronous dipoles. The recursive subspace projection procedure that they introduce here uses the metric of canonical or subspace correlations as a multidimensional form of correlation analysis between the model subspace and the data subspace, by recursively computing subspace correlations, the authors build up a model for the sources which account for a given set of data. They demonstrate here how R-MUSIC can easily extract multiple asynchronous dipolar sources that are difficult to find using the original MUSIC scan. The authors then demonstrate R-MUSIC applied to the more general IT model and show results for combinations of fixed, rotating, and synchronous dipoles.
STAT3: A multifaceted oncogene (2006)

Signal transducers and activators of transcription (STAT) proteins are a family of transcription factors first characterized for their role in cytokine signaling. These versatile proteins contain a site for specific tyrosine phosphorylation, a modification that results in a conformational rearrangement and dimerization through phosphotyrosine–SH2 domain interactions (1). Once activated in this manner, phosphorylated STAT protein dimers accumulate in the cell nucleus, bound to enhancer elements of target genes. STAT proteins were first characterized as intermediaries in IFN signaling, a growth inhibitory cytokine pathway involved in antiviral and innate immune responses. However, as additional members of this protein family were discovered, they caught the eyes of cancer biologists as potential mediators of growth control and possibly oncogenic events. In particular, it became recognized that STAT3 and, to a lesser extent, STAT5 were stimulated by classic growth-promoting signals, such as activated growth factor receptors. Even more compelling were the seminal observations that STAT3 was a substrate for the catalytic activity of the tyrosine kinase oncoprotein v-Src (2) and that phosphorylated STAT3 accumulated in many human cancers, leading to the hypothesis that activated STAT3 is an oncogene (3). A considerable amount of experimental and clinical observations have now confirmed such a role for STAT3, and a remarkable degree of diversity has been uncovered for the molecular mechanisms at the basis of STAT3 action. Much early work has focused on direct growth-control and cell survival …
Human NK Cells Are Alerted to Induction of p53 in Cancer Cells by Upregulation of the NKG2D Ligands ULBP1 and ULBP2 (2011)

Natural killer (NK) cells are immune cells sensing and eliminating foreign, stressed, transformed, and senescent cells through specialized surface receptors, such as NKG2D, that interacts with several virus- or stress-inducible ligands, including ULBP1 and -2, which are expressed on target cell surfaces. For example, induction of DNA damage or cellular senescence pathways in tumor cells led to upregulation of NKG2D ligands that activate NK cells. Although, both pathways activate p53, the relationship of p53 activation to upregulation of NKG2D ligands has not been addressed. In this study, we report that induction of wild-type p53, but not mutant p53, strongly upregulated mRNA and cell surface expression of ULBP1 and -2, whereas expression of other NK cell ligands was not affected. We defined intronic p53-responsive elements in these two novel p53 target genes. Coculture of wild-type p53-induced human tumor cells with primary human NK cells enhanced NKG2D-dependent degranulation and IFN-γ production by NK cells. Accordingly, treatment of certain wild-type p53-expressing tumor cell lines with the p53-reactivating small molecular compound RITA resulted in upregulation of ULBP2 mRNA and cell surface protein expression. Taken together, our findings define the involvement of p53 in the regulation of specific NKG2D ligands that enhance NK cell-mediated target recognition. One implication of our work is that activating p53 after adoptive transfer of NK cells might constitute an effective combinatorial strategy of NK cell-based immunochemotherapy in cancers in which wild-type p53 function is preserved.
Enrichment of erythrocytes of fetal origin from adult-fetal blood mixtures via selective hemolysis of adult blood cells: an aid to antenatal diagnosis of hemoglobinopathies (1976)

Red cell lysis in isotonic solutions containing NH4Cl, NH4HCO3, and a carbonic anhydrase enzyme inhibitor (acetazolamide) is a function of erythrocyte enzyme activity and permeability of cells to the inhibitor. Erythrocyte carbonic anhydrase activity is at least fivefold greater and acetazolamide permeability about tenfold less for adults than for newborns. In this setting, greater than 99.9% of red cells from adults can be hemolyzed at a time when greater than 25% of those from newborns remain intact. This easily applied method may be useful when antenatal diagnosis of hemoglobinopathies is otherwise precluded by contaimination with maternal erythrocytes. The feasibility of differential hemolysis via NH4Cl--HCO3-mediated, acetazolamide- modulated reactions is shown by the successful isolation of the few fetal-origin erythrocytes present in grossly nonbloody amniotic fluids and, in one instance, by approximately 3300-fold enrichment of apparently authentic fetal-origin red cells from the arm blood of a woman in her 18th wk of pregnancy.
Plume Emission, Shock Wave and Surface Wave Formation During Excimer Laser Ablation of the Cornea (1993)

Excimer lasers are now used for corneal surgery; however, the physical processes occurring during photoablation of the cornea are incompletely understood. High speed laser-based photographic arrangement was constructed. The temporal resolution was better than 1 ns. The setup could work as a Schlieren arrangement, which is sensitive to the refractive index change caused by the shock wave propagating in the air above the eye. With minor changes the setup was converted into a shadowgraph, which could detect the ablation plume and the waves propagating on the surface of the eye. Due to the impact of the excimer laser pulse onto the surface of the cornea, a shock wave was generated in the air. The shadowgraph clearly showed the ejection of the ablated cornea. The ejection velocity of the plume was found to be over 600 m/s. It was shown for the first time that the recoil forces of the plume are generating a wave on the surface of the eye. The laser-based high speed photographic arrangement is a powerful arrangement in the study of physical effects occurring during photoablation of the cornea.
Representing hospital events as complex conditionals. (1995)

We have developed an approach to medical knowledge representation whereby simple medical concepts are combined to yield complex statements of testable medical logic. The logic is created from a small number of generic medical concepts that are instantiated and combined to create the rules. Rule writing is done through a rule editor and requires knowledge of the system's data dictionaries, though no programming is required. We have used the approach to create a large knowledge base including panic lab alerting rules, drug-laboratory interaction alerting rules, an adverse drug event monitor, and a drug-age interaction detection program. The rules have been used as part of an alerting system and for data collection to determine the frequency of events of interest. The scheme is extensible and yields a readable form of the created knowledge. The scheme holds great promise as a durable form of medical knowledge representation.
Gene Silencing Using Adenoviral RNAi Vector in Vascular Smooth Muscle Cells and Cardiomyocytes (2005)

RNA interference (RNAi) is a new and rapidly progressing technology for facilitating functional gene silencing. To perform highly efficient RNAi in cardiomyocytes, vascular smooth muscle cells, and vascular endothelial cells, which are known to have very low transfection efficiency, adenovirus-mediated RNAi was employed. The effects of RNAi on GAPDH transcripts were successfully reduced by nearly 90% in the primary cultured cells, indicating that adenovirus-mediated gene silencing is a promising technique for gene silencing in cardiovascular studies. This chapter describes general guidelines for selecting RNAi target sites, construction of a shuttle vector encoding short hairpin RNAi, and generation of recombinant adenovirus.
Validation of a Verbally Administered Numerical Rating Scale of Acute Pain for Use in the Emergency Department (2003)

The findings suggest that the verbally administered NRS can be substituted for the VAS in acute pain measurement.
Transient Anomalous Diffusion of Telomeres in the Nucleus of Mammalian Cells (2009)

We measured individual trajectories of fluorescently labeled telomeres in the nucleus of eukaryotic cells in the time range of 10(-2)-10(4)sec by combining a few acquisition methods. At short times the motion is subdiffusive with r2 approximately talpha and it changes to normal diffusion at longer times. The short times diffusion may be explained by the reptation model and the transient diffusion is consistent with a model of telomeres that are subject to a local binding mechanism with a wide but finite distribution of waiting times. These findings have important biological implications with respect to the genome organization in the nucleus.
Formation of Aroma Compounds from Ribose and Cysteine during the Maillard Reaction (2003)

The headspace volatiles produced from a phosphate-buffered solution (pH 5) of cysteine and a 1 + 1 mixture of ribose and [(13)C(5)]ribose, heated at 95 degrees C for 4 h, were examined by headspace SPME in combination with GC-MS. MS data indicated that fragmentation of ribose did not play a significant role in the formation of the sulfur aroma compounds 2-methyl-3-furanthiol, 2-furfurylthiol, and 3-mercapto-2-pentanone in which the carbon skeleton of ribose remained intact. The methylfuran moiety of 2-methyl-3-(methylthio)furan originated from ribose, whereas the methylthio carbon atoms came partly from ribose and partly from cysteine. In 3-mercapto-2-butanone one carbon unit was split from the ribose chain. On the other hand, all carbon atoms in 3-thiophenethiol stemmed from cysteine. In another trial cysteine, 4-hydroxy-5-methyl-3(2H)-furanone and [(13)C(5)]ribose were reacted under the same conditions. The resulting 2-methyl-3-furanthiol was mainly (13)C(5)-labeled, suggesting that it stems from ribose and that 4-hydroxy-5-methyl-3(2H)-furanone is unimportant as an intermediate. Whereas 2-mercapto-3-pentanone was found unlabeled and hence originated from 4-hydroxy-5-methyl-3(2H)-furanone, its isomer 3-mercapto-2-pentanone was formed from both 4-hydroxy-5-methyl-3(2H)-furanone and ribose. A new reaction pathway from ribose via its 1,4-dideoxyosone is proposed, which explains both the formation of 2-methyl-3-furanthiol without 4-hydroxy-5-methyl-3(2H)-furanone as an intermediate and a new way to form 3-mercapto-2-pentanone.
Combinatorial Selection, Inhibition, and Antiviral Activity of DNA Thioaptamers Targeting the RNase H Domain of HIV-1 Reverse Transcriptase (2005)

Despite the key role played by the RNase H of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT) in viral proliferation, only a few inhibitors of RNase H have been reported. Using in vitro combinatorial selection methods and the RNase H domain of the HIV RT, we have selected double-stranded DNA thioaptamers (aptamers with selected thiophosphate backbone substitutions) that inhibit RNase H activity and viral replication. The selected thioaptamer sequences had a very high proportion of G residues. The consensus sequence for the selected thioaptamers showed G clusters separated by single residues at the 5'-end of the sequence. Gel electrophoresis mobility shift assays and nuclear magnetic resonance spectroscopy showed that the selected thioaptamer binds to the isolated RNase H domain, but did not bind to a structurally similar RNase H from Escherichia coli. The lead thioaptamer, R12-2, showed specific binding to HIV-1 RT with a binding constant (K(d)) of 70 nM. The thioaptamer inhibited the RNase H activity of intact HIV-1 RT. In cell culture, transfection of thioaptamer R12-2 (0.5 microg/mL) markedly inhibited viral production and exhibited a dose response of inhibition with R12-2 concentrations ranging from 0.03 to 2.0 microg/mL (IC(50) < 100 nM). Inhibition was also seen across a wide range of virus inoculum, ranging from a multiplicity of infection (moi) of 0.0005 to 0.05, with a reduction of the level of virus production by more than 50% at high moi. Suppression of virus was comparable to that seen with AZT when moi <or= 0.005.
An Improved Method For Computerized Tomography-Planned Transperineal 125 Iodine Prostate Implants (1991)

Transperineal 125iodine implants of the prostate can be performed with ultrasound guidance, a simple technique that has met with widespread acceptance. However, ultrasound does not allow good visualization of the pubic bones in relation to the pelvic outlet, and the pubic bones may interfere with needle placement in the anterior peripheral aspect of the prostate. Adequate irradiation of the entire periphery of the prostate is important to assure tumor control, since most tumors are multicentric and may involve the anterior aspect of the prostate. A computerized tomography-based treatment planning procedure that allows for angulation of transperineal needles to avoid the pubic bones and still reaches the most peripheral aspects of the gland is described. The technique also allows for the use of transrectal ultrasound and fluoroscopy to verify correct needle placement in the prostate at the procedure. Early treatment results, based on prostate specific antigen and regression of palpable tumors, are encouraging.
Natural killer cells in the synovial fluid of rheumatoid arthritis patients exhibit a CD56bright,CD94bright,CD158negative phenotype (2003)

We identified a novel phenotype of SF NK cells that is of potential significance in RA. Experiments are now under way to determine the function of these SF NK cells and their potential role in RA.
PaperPoint (2007)

Recent developments in digital pen and paper solutions enable, not only the digital capture of handwriting, but also paper to be used as an interactive medium that links to digital information and services. We present a tool that builds on technologies for interactive paper to enable PowerPoint presentations to be controlled from printed slide handouts. Furthermore, slides can be easily annotated during presentations by simply drawing on the printed version of the slide. As well as discussing the advantages of such a paper-based interface and initial findings on its use, we describe how we were also able to exploit it to provide a general prototyping tool for interactive paper applications.
Antisense RNA Control in Bacteria, Phages, and Plasmids (1994)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Phenothiazine analgesia--fact or fantasy? (1979)

Double-blind clinical trials involving the use of phenothiazines as analgesics or potentiators of analgesics (aspirin, meperidine, morphine sulfate) and adverse effects of phenothiazines are reviewed and evaluated. Promethazine, promazine and propiomazine were not found to possess analgesic or potentiating properties. One chlorpromazine study contained important design and reporting deficiencies which precluded a recommendation for use of chlorpromazine in the treatment of pain. Methotrimeprazine was determined by numerous authors to have analgesic properties; however, most of the studies also were deficient in design or data presented, or both. Adverse reactions to phenothiazines, including hypotension, sedation, drowsiness, extrapyramidal symptoms, tardive dyskinesia, cardiac toxicity and agranulocytosis, are often more common and severe than those attributed to narcotic analgesics. Because of the lack of data supportive of analgesic activity and the adverse reactions associated with phenothiazines, use of these agents in the management of pain should be discouraged. The prophylactic use of phenothiazine for narcotic analgesic-induced emesis also is, in most cases, a questionable practice.
Amphoteric Linear Poly(amido-amine)s as Endosomolytic Polymers:  Correlation between Physicochemical and Biological Properties (2000)

Five poly(amido-amine)s (PAAs) carrying two ter-amino groups and one carboxyl group per repeating unit were prepared by hydrogen-transfer polyaddition of 2-methylpiperazine (ISA 23), 1,2-bis(N-methylamino)ethane (DMEDA-BAC), 1,2-bis(N-ethylamino)ethane (DEEDA-BAC, 1,3-bis(N-methylamino)propane (DMEPDA-BAC), or 1,6-bis(N-methylamino)hexane (DMEXA-BAC), in each case to 2,2-bis(acrylamido)acetic acid (BAC). The resultant PAAs had an Mn in the range 7 985−24 980 g/mole and an Mw in the range 11 420−42 710 g/mole. Considerable differences were observed in the basicity of the amino groups present (log K°1 = 7.5−9.5; log K°2 = 3.2−8.4), whereas the log K°3 value (2−3) of the carboxyl groups was consistent with that of a fairly strong acid. DEEDA-BAC, DMEDA-BAC, and ISA 23 were nontoxic (IC50 > 5 mg/mL). Those PAAs with the highest log K°2 values were more cytotoxic (IC50 = 3.55 mg/mL for DMEPDA-BAC, and IC50 = 0.23 m/mL for DMEXA-BAC). All the PAAs displayed pH-dependent haemolysis (most lytic at pH 5.5), consistent with their proposed use as endosomolytic polymers.