gebhart/patrepeval huggingface dataset:
Human Genome Sequencing in Health and Disease (2011)

Following the "finished," euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges.
GFP‐like chromoproteins as a source of far‐red fluorescent proteins (2001)

We have employed a new approach to generate novel fluorescent proteins (FPs) from red absorbing chromoproteins. An identical single amino acid substitution converted novel chromoproteins from the species Anthozoa (Heteractis crispa, Condylactis gigantea, and Goniopora tenuidens) into far-red FPs (emission lambda(max)=615-640 nm). Moreover, coupled site-directed and random mutagenesis of the chromoprotein from H. crispa resulted in a unique far-red FP (HcRed) that exhibited bright emission at 645 nm. A clear red shift in fluorescence of HcRed, compared to drFP583 (by more than 60 nm), makes it an ideal additional color for multi-color labeling. Importantly, HcRed is excitable by 600 nm dye laser, thus promoting new detection channels for multi-color flow cytometry applications. In addition, we generated a dimeric mutant with similar maturation and spectral properties to tetrameric HcRed.
Promising tumor‐associated antigens for future prostate cancer therapy (2009)

Prostate cancer (CaP) is one of the most prevalent malignant diseases among men in Western countries. There is currently no cure for metastatic castrate-resistant CaP, and median survival for these patients is about 18 months; the high mortality rate seen is associated with widespread metastases. Progression of CaP from primary to metastatic disease is associated with several molecular and genetic changes that can affect the expression of specific tumor-associated antigens (TAAs) or receptors on the cell surface. Targeting TAAs is emerging as an area of promise for controlling late-stage and recurrent CaP. Several reviews have summarized the progress made in targeting signaling pathways for CaP but will not be discussed here. We describe some important CaP TAAs. These include prostate stem-cell antigen, prostate-specific membrane antigen, MUC1, epidermal growth factor receptor, platelet-derived growth factor and its receptor, urokinase plasminogen activator and its receptor, and extracellular matrix metalloproteinase inducer. We summarize recent advancements in our understanding of their role in CaP metastasis, as well as potential therapeutic options for targeting CaP TAAs. We also discuss the origin, identification, and characterization of prostate cancer stem cells (CSCs) and the potential benefits of targeting prostate CSCs to overcome chemoresistance and CaP recurrence.
Nucleic Acid Template-Directed Assembly of Metallosalen−DNA Conjugates (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNucleic Acid Template-Directed Assembly of Metallosalen−DNA ConjugatesJennifer L. Czlapinski and Terry L. SheppardView Author Information Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113 Cite this: J. Am. Chem. Soc. 2001, 123, 35, 8618–8619Publication Date (Web):August 10, 2001Publication History Received17 May 2001Revised14 July 2001Published online10 August 2001Published inissue 1 September 2001https://pubs.acs.org/doi/10.1021/ja0162212https://doi.org/10.1021/ja0162212rapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1445Altmetric-Citations129LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Biopolymers,Conjugate acid-base pairs,Genetics,Nucleic acids,Peptides and proteins Get e-Alerts
Étude internationale des curricula (1996)

Dans le cadre des enquêtes menées par l’IEA, la troisième enquête internationale sur les mathématiques et les sciences a été l’occasion d’une mise au point de techniques d’analyses facilitant l’étude des curricula, et, plus spécifiquement, le curriculum formel (intented curriculum). Ces techniques qui représentent une innovation importante pour la recherche éducative, font l’objet d’une présentation dans cet article.
Formation of D‐alanyl‐lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes (2002)

The dlt operon of Gram-positive bacteria comprises four genes (dltA, dltB, dltC and dltD) that catalyse the incorporation of D-alanine residues into the cell wall-associated lipoteichoic acids (LTAs). In this work, we characterized the dlt operon of Listeria monocytogenes and constructed a D-Ala-deficient LTA mutant by inactivating the first gene (dltA) of this operon. The DltA- mutant did not show any morphological alterations and its growth rate was similar to that of the wild-type strain. However, it exhibited an increased susceptibility to the cationic peptides colistin, nisin and polymyxin B. The virulence of the DltA- mutant was severely impaired in a mouse infection model (4 log increase in the LD50) and, in vitro, the adherence of the mutant to various cell lines (murine bone marrow-derived macrophages and hepatocytes and a human epithelial cell line) was strongly restricted, although the amounts of surface proteins implicated in virulence (ActA, InlA and InlB) remains unaffected. We suggest that the decreased adherence of the DltA- mutant to non-phagocytic and phagocytic cells might be as a result of the increased electronegativity of its charge surface and/or the presence at the bacterial surface of adhesins possessing altered binding activities. These results show that the D-alanylation of the LTAs contributes to the virulence of the intracellular pathogen L. monocytogenes.
Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors (1999)

Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an important event in the conversion of extracellular signals into a cellular response. However, the existence of multiple MAP kinases which phosphorylate similar phosphoacceptor motifs poses a problem in maintaining substrate specificity and hence the correct biological response. Both the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) subfamilies of MAP kinases use a second specificity determinant and require docking to their transcription factor substrates to achieve maximal substrate activation. In this study, we demonstrate that among the different MAP kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2. The efficiency of phosphorylation in vitro and transcriptional activation in vivo of MEF2A and MEF2C by these p38 subtypes requires the presence of a kinase docking domain (D-domain). Furthermore, the D-domain from MEF2A is sufficient to confer p38 responsiveness on different transcription factors, and reciprocal effects are observed upon the introduction of alternative D-domains into MEF2A. These results therefore contribute to our understanding of signalling to MEF2 transcription factors and demonstrate that the requirement for substrate binding by MAP kinases is an important facet of three different subclasses of MAP kinases (ERK, JNK, and p38).
Studies on 1,2,3,-triazoles. 10. Synthesis and antiallergic properties of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazoles and their S-oxides (1984)

Selected derivatives of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole, a new heterocyclic ring system, and their S-oxides have been prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. Several of the compounds show intravenous potencies similar to or greater than that of disodium cromoglycate, the most potent being 6,7-dimethyl-9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole and its 4,4-dioxide.
From Prelife to Life: How Chemical Kinetics Become Evolutionary Dynamics (2012)

Life is that which evolves. Living systems are the products of evolutionary processes and can undergo further evolution. A crucial question for the origin of life is the following: when do chemical kinetics become evolutionary dynamics? In this Account, we review properties of "prelife" and discuss the transition from prelife to life. We describe prelife as a chemical system where activated monomers can copolymerize into macromolecules such as RNA. These macromolecules carry information, and their physical and chemical properties depend to a certain extent on their particular sequence of monomers. We consider prelife as a logical precursor of life, where macromolecules are formed by copolymerization, but they cannot replicate. Prelife can undergo "prevolutionary dynamics", including processes such as mutation, selection, and cooperation. Prelife selection, however, is blunt: small differences in rate constants lead to small differences in abundance. Life emerges with the ability of replication. In the resulting evolutionary dynamics, selection is sharp: small differences in rate constants can lead to large differences in abundance. We also study the competition of different "prelives" and find that there can be selection for those systems that ultimately give rise to replication. The transition from prelife to life can occur over an extended period of time. Instead of a single moment that marks the origin of life, prelife may have seeded many attempts for the origin of life. Eventually life takes over and destroys prelife.
Delineation of T-Wave in ECG by Wavelet Transform Using Multiscale Differential Operator (2006)

This paper proposes an improved wavelet-based method for the delineation of T wave in the electrocardiogram by using multiscale dif-operator (MDO). MDO was employed to automatically categorize the T wave into one of the three categories of T wave morphologies and to improve the precision of T wave delineation for each category. The new algorithm was evaluated on QT database (QTDB) and new annotations of 2160 beats from QTDB were performed by two cardiologists. To evaluate the performance of the wave delineation, the time differences between automatic detection versus cardiologists' annotations and intercardiologist differences were measured. The new algorithm can attain better results than the previous methods by achieving the smallest standard deviation of the differences and qualifying the strict error criterion for T-off measurement. This new algorithm also exhibited excellent T wave categorization agreement with the cardiologists, resulting in kappa values above 0.75.
HIV-1 pol gene variation is sufficient for reconstruction of transmissions in the era of antiretroviral therapy (2004)

Despite its genetic conservation, the HIV-1 pol gene holds sufficient variability to permit the phylogenetic reconstruction of transmissions. Identical clusters were obtained whichever of the three principal genes is considered and no bias was induced by the presence of drug resistance mutations. These findings demonstrate the important epidemiological information inherent within routinely collected laboratory data, which can assist in estimating rates of recent HIV-1 transmission within a population.
Purification, Cloning, and Expression of Ciliary Neurotrophic Factor (CNTF) (1989)

Ciliary neurotrophic factor (CNTF) is one of a small number of proteins with neurotrophic activities distinct from nerve growth factor (NGF). CNTF has now been purified and cloned and the primary structure of CNTF from rabbit sciatic nerve has been determined. Biologically active CNTF has been transiently expressed from a rabbit complementary DNA clone. CNTF is a neural effector without significant sequence homologies to any previously reported protein.
Second-harmonic generation frequency-resolved optical gating in the single-cycle regime (1999)

The problem of measuring broad-band femtosecond pulses by the technique of second-harmonic generation frequency-resolved optical gating (SHG FROG) is addressed. We derive the full equation for the FROG signal, which is valid even for single-optical-cycle pulses. The effect of the phase mismatch in the second-harmonic crystal, the implications of the beam geometry, and the frequency-dependent variation of the nonlinearity are discussed in detail. Our numerical simulations show that, under carefully chosen experimental conditions and with a proper spectral correction of the data, the traditional FROG inversion routines work well even in the single-cycle regime. The developed description of the SHG FROG signal was applied to measure the white-light continuum pulses in the spectral region of 500-1100 nm. The obtained spectral phase of these pulses served as a target function for the pulse compressor design. The pulses produced by compression around 800 nm were also characterized by SHG FROG. The resulting pulse duration measures 4.5 fs which corresponds to /spl sim/2.5 optical cycles.
Towards Si1−xGex quantum-well resonant-state terahertz laser (2001)

We report on the experimental evidence for terahertz (THz) lasing of boron-doped strained Si1−xGex quantum-well structures. The lasing arises under strong electric fields (300–1500 V/cm) applied parallel to interfaces. The spectrum of THz stimulated emission is presented showing the lasing wavelength near 100 μm and the modal structure caused by a resonator. The mechanism of population inversion is based on the formation of resonant acceptor states in strained SiGe layer.
Performance measurement and evaluation of online information systems (1985)

Article Free Access Share on Performance measurement and evaluation of online information systems Author: John E. Tolle OCLC, Online Computer Library Center, Inc. OCLC, Online Computer Library Center, Inc.View Profile Authors Info & Claims CSC '85: Proceedings of the 1985 ACM thirteenth annual conference on Computer ScienceMarch 1985 Pages 196–203https://doi.org/10.1145/320599.320677Online:01 March 1985Publication History 1citation377DownloadsMetricsTotal Citations1Total Downloads377Last 12 Months3Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Effects of Non-Thermal Plasma on Mammalian Cells (2011)

Thermal plasmas and lasers have been widely used in medicine to cut, ablate and cauterize tissues through heating; in contrast, non-thermal plasma produces no heat, so its effects can be selective. In order to exploit the potential for clinical applications, including wound healing, sterilization, blood coagulation, and cancer treatment, a mechanistic understanding of the interaction of non-thermal plasma with living tissues is required. Using mammalian cells in culture, it is shown here that non-thermal plasma created by dielectric barrier discharge (DBD) has dose-dependent effects that range from increasing cell proliferation to inducing apoptosis. It is also shown that these effects are primarily due to formation of intracellular reactive oxygen species (ROS). We have utilized γ-H2AX to detect DNA damage induced by non-thermal plasma and found that it is initiated by production of active neutral species that most likely induce formation of organic peroxides in cell medium. Phosphorylation of H2AX following non-thermal plasma treatment is ATR dependent and ATM independent, suggesting that plasma treatment may lead to replication arrest or formation of single-stranded DNA breaks; however, plasma does not lead to formation of bulky adducts/thymine dimers.
Site-Specific Integration of Transgenes in Soybean via Recombinase-Mediated DNA Cassette Exchange (2009)

A targeting method to insert genes at a previously characterized genetic locus to make plant transformation and transgene expression predictable is highly desirable for plant biotechnology. We report the successful targeting of transgenes to predefined soybean (Glycine max) genome sites using the yeast FLP-FRT recombination system. First, a target DNA containing a pair of incompatible FRT sites flanking a selection gene was introduced in soybean by standard biolistic transformation. Transgenic events containing a single copy of the target were retransformed with a donor DNA, which contained the same pair of FRT sites flanking a different selection gene, and a FLP expression DNA. Precise DNA cassette exchange was achieved between the target and donor DNA via recombinase-mediated cassette exchange, so that the donor DNA was introduced at the locus previously occupied by the target DNA. The introduced donor genes expressed normally and segregated according to Mendelian laws.
Separation technologies for stem cell bioprocessing (2012)

Stem cells have been the focus of an intense research due to their potential in Regenerative Medicine, drug discovery, toxicology studies, as well as for fundamental studies on developmental biology and human disease mechanisms. To fully accomplish this potential, the successful application of separation processes for the isolation and purification of stem cells and stem cell-derived cells is a crucial issue. Although separation methods have been used over the past decades for the isolation and enrichment of hematopoietic stem/progenitor cells for transplantation in hemato-oncological settings, recent achievements in the stem cell field have created new challenges including the need for novel scalable separation processes with a higher resolution and more cost-effective. Important examples are the need for high-resolution methods for the separation of heterogeneous populations of multipotent adult stem cells to study their differential biological features and clinical utility, as well as for the depletion of tumorigenic cells after pluripotent stem cell differentiation. Focusing on these challenges, this review presents a critical assessment of separation processes that have been used in the stem cell field, as well as their current and potential applications. The techniques are grouped according to the fundamental principles that govern cell separation, which are defined by the main physical, biophysical, and affinity properties of cells. A special emphasis is given to novel and promising approaches such as affinity-based methods that take advantage of the use of new ligands (e.g., aptamers, lectins), as well as to novel biophysical-based methods requiring no cell labeling and integrated with microscale technologies.
Dual-frequency planar inverted-F antenna (1997)

Cellular telephone handsets are now being designed to have dual-mode capabilities. In particular, there is a requirement for internal antennas for GSM and DCS1800 systems. This paper describes a novel planar dual-band inverted-F antenna for cellular handsets, which operates at the 0.9-GHz and 1.8-GHz bands. The dual-band antenna has almost the same size as a conventional inverted-F antenna operating at 0.9 GHz and has an isolation between bands of better than 17 dB. The bandwidths of the antenna are close to those required for the above systems. Good dual-band action is also obtained for other frequency ratios in the range of 1.3-2.4. Studies also show that the dual-band antenna can operate with one or two feeds. A finite-difference time-domain analysis has been shown to give calculated results close to those measured.
Antagonism of the Stat3–Stat3 Protein Dimer with Salicylic Acid Based Small Molecules (2011)

More than 50 new inhibitors of the oncogenic Stat3 protein were identified through a structure-activity relationship (SAR) study based on the previously identified inhibitor S3I-201 (IC₅₀ =86 μM, K(i) >300 μM). A key structural feature of these inhibitors is a salicylic acid moiety, which, by acting as a phosphotyrosine mimetic, is believed to facilitate binding to the Stat3 SH2 domain. Several of the analogues exhibit higher potency than the lead compound in inhibiting Stat3 DNA binding activity, with an in vitro IC₅₀ range of 18.7-51.9 μM, and disruption of Stat3-pTyr peptide interactions with K(i) values in the 15.5-41 μM range. One agent in particular exhibited potent inhibition of Stat3 phosphorylation in both breast and multiple myeloma tumor cells, suppressed the expression of Stat3 target genes, and induced antitumor effects in tumor cells harboring activated Stat3 protein.
Molecular Approach to Adenosine Receptors: Receptor-Mediated Mechanisms of Tissue Protection (2001)

Adenosine accumulation during ischemia and inflammation protects tissues from injury. In ischemic tissues adenosine accumulates due to inhibition of adenosine kinase, and in inflamed tissues adenosine is formed from adenine nucleotides that are released from many cells including platelets, mast cells, nerves, and endothelium. Nucleotides are rapidly converted to adenosine by a family of ecto-nucleotidases including CD39 and CD73. Activation of A(1) and possibly A(3) adenosine receptors (ARs) protects heart and other tissues by preconditioning through a pathway including protein kinase C and mitochondrial K(ATP) channels. Activation of A(2A) receptors limits reperfusion injury by inhibiting inflammatory processes in neutrophils, platelets, macrophages and T cells. Adenosine produces proinflammatory responses mediated by receptors that vary among species; A(3) and A(2B) receptors mediate degranulation of rodent and human or canine mast cells, respectively. Novel adenosine receptor subtype-selective ligands have recently been developed. These include MRS1754 (A(2B) blocker), MRS1220 (A(3) blocker), MRE 3008F20 (human A(3) blocker), MRS1523 (rat A(3) blocker), and ATL146e (A(2A) agonist). These new pharmacologic tools will help investigators to sort out how adenosine protects tissues from injury and to identify new therapeutic agents that hold promise for the treatment of inflammatory and ischemic diseases.
Interferon-γ-deficient mice are resistant to the development of alopecia areata (2006)

IFNgamma(-/-) mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated Th1 activation in the induction of AA.