gebhart/patrepeval huggingface dataset:
Synthesis Of Novel Graft Copolymers Of Hyaluronan, Polyethyleneglycol And Polylactic Acid (2007)

New amphiphilic derivatives of hyaluronic acid(HA) have been synthesized by grafting of both hydrophobic and hydrophilic branches, such as polylactic(PLA) and polyethylene glycol(PEG) chains. Graft copolymers so obtained, named PEG-g-HA-g-PLA have been characterized by spectral analysis that allowed to determine the grafting degree in PLA and PEG chains. Self assembling properties evaluated in aqueous media resulted to be dependent on the molar amount of PLA and PEG linked to HA. Further studies are in progress to evaluate other physicochemical properties of these materials and their biomedical and pharmaceutical applications.
Whole-organism lineage tracing by combinatorial and cumulative genome editing (2016)

Multicellular systems develop from single cells through distinct lineages. However, current lineage-tracing approaches scale poorly to whole, complex organisms. Here, we use genome editing to progressively introduce and accumulate diverse mutations in a DNA barcode over multiple rounds of cell division. The barcode, an array of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 target sites, marks cells and enables the elucidation of lineage relationships via the patterns of mutations shared between cells. In cell culture and zebrafish, we show that rates and patterns of editing are tunable and that thousands of lineage-informative barcode alleles can be generated. By sampling hundreds of thousands of cells from individual zebrafish, we find that most cells in adult organs derive from relatively few embryonic progenitors. In future analyses, genome editing of synthetic target arrays for lineage tracing (GESTALT) can be used to generate large-scale maps of cell lineage in multicellular systems for normal development and disease.
Growth of factor-dependent hemopoietic precursor cell lines. (1980)

Cell lines have been produced from long-term cultures of mouse bone marrow that require a factor, present in WEHI-3 conditioned medium (CM) or in spleen CM, for their sustained growth. The cell lines were obtained from nonvirus-treated cultures, are nonleukemic, maintain a normal karyotype, and form colonies showing granulocyte maturation when plated in soft agar. Granulocyte/macrophage (GM) colony-stimulating factor is not the inductive moiety involved in the maintenance of proliferation of these cells. It is suggested that the cell lines represent a self-renewing population of cells ancestral to GM colony-forming cells, which may be responding to a hitherto unrecognized regulator.
Isolation and sequence analysis of cDNAs for the major potato tuber protein, patatin (1984)

A cDNA library from membrane-bound poly(A)+ mRNA of developing potato tubers was constructed and two classes of essentially full-length cDNA clones for a precursor to the major tuber glycoprotein, patatin were isolated. Sequence analysis shows that the two classes are approximately 99% homologous and correspond to the two major species of patatin identified previously by NH2-terminal amino acid sequence analysis. Sequence analysis also predicts that patatin is synthesized with a 23 amino acid signal sequence. Northern blot analysis shows that patatin mRNAs are 1550 +/- 50 nucleotides in length and are normally not present in polyribosomal or total RNA from stems or leaves.
Production of a functional eukaryotic enzyme in Escherichia coli: cloning and expression of the yeast structural gene for imidazole-glycerolphosphate dehydratase (his3). (1977)

A cloned segment of yeast DNA containing the structural gene for imidazoleglycerolphosphate dehydratase (D-erythro-imidazoleglycerolphosphate hydro-lase, EC 4.2.1.19) is transcribed and translated in Escherichia coli with sufficient fidelity to produce functional enzyme. This segment of yeast DNA was isolated as a viable molecular hybrid of bacteriophage lambda (lambdagt-Sc2601) which complements a nonrevertible hisB auxotroph of E. coli lacking dehydratase activity. The equivalent segments of DNA cloned from two independent his3 mutants of yeast lacking IGP dehydratase activity do not complement the hisB auxotroph. The two nonfunctional his3 alleles cloned in bacteriophage lambda can be recombined in E. coli to generate a hybrid phage which complements the hisB auxotroph. The dehydratase activity produced in E. coli by the cloned segment of yeast DNA strongly resembles the activity found in yeast.
Plaque Formation in Agar by Single Antibody-Producing Cells (1963)

Distinct plaques, each of which is due to the release of hemolysin by a single antibody-forming cell, are revealed by complement after incubation, in an agar layer, of a mixture of sheep red cells and lymphoid cells from a rabbit immunized with sheep red cells.
Preparation and use of C2-symmetric bis(phospholanes): production of .alpha.-amino acid derivatives via highly enantioselective hydrogenation reactions (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation and use of C2-symmetric bis(phospholanes): production of .alpha.-amino acid derivatives via highly enantioselective hydrogenation reactionsMark J. Burk, John E. Feaster, William A. Nugent, and Richard L. HarlowCite this: J. Am. Chem. Soc. 1993, 115, 22, 10125–10138Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/ja00075a031https://doi.org/10.1021/ja00075a031research-articleACS PublicationsRequest reuse permissionsArticle Views5298Altmetric-Citations596LEARN 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 (3)»Supporting Information Supporting Information Get e-Alerts
Triple-negative breast cancer: treatment challenges and solutions (2016)

Triple-negative breast cancers (TNBCs) are defined by the absence of estrogen and progesterone receptors and the absence of HER2 overexpression. These cancers represent a heterogeneous breast cancer subtype with a poor prognosis. Few systemic treatment options exist besides the use of chemotherapy (CT). The heterogeneity of the disease has limited the successful development of targeted therapy in unselected patient populations. Currently, there are no approved targeted therapies for TNBC. However, intense research is ongoing to identify specific targets and develop additional and better systemic treatment options. Standard adjuvant and neoadjuvant regimens include anthracyclines, cyclophosphamide, and taxanes. Platinum-based CT has been proposed as another CT option of interest in TNBC. We review the role of this therapy in general, and particularly in patients carrying BRCA germ-line mutations. Available data concerning the role of platinum-based CT in TNBC were acquired primarily in the neoadjuvant setting. The routine use of platinum-based CT is not yet recommended by available guidelines. Many studies have reported the molecular characterization of TNBCs. Several actionable targets have been identified. Novel therapeutic strategies are currently being tested in clinical trials based on promising results observed in preclinical studies. These targets include androgen receptor, EGFR, PARP, FGFR, and the angiogenic pathway. We review the recent data on experimental drugs in this field. We also discuss the recent data concerning immunologic checkpoint inhibitors.
Automatic Induction of Rules of e-mail Classification (2001)

Many users receive large amounts of email. Since a substantial part of that mail is kept for future reference, it is unsurprising that many mail tools allow users to create filtering rules that automatically do actions like saving mail in suitable folders. Unfortunately, most users do not make much use of this facility. This paper describes the i-ems project which explores approaches to building a system to assist users in managing electronic mail. It does this by learning rules for classifying email so that it can assist the user in filing messages. This classification is also a precondition to automated action on behalf of the user and we are particularly interested in using it as part of a smart personal assistant. We begin with a review of similar work and identify the core issues for the i-ems project. We relate the past work to classic information retrieval work in text classification and discuss the major new issues that we need to address. We present a simple user interface which automatically learns rules to improve the user&amp;apos;s overall interaction with the email manager. We also present empirical results which compare four different learning approaches as email is progressively provided.
Molecular evolution of flower development: diversification of the plant MADS-box regulatory gene family. (1995)

Floral homeotic genes that control the specification of meristem and organ identity in developing flowers have been isolated from both Arabidopsis thaliana and Antirrhinum majus. Most of these genes belong to a large family of regulatory genes and possess a characteristic DNA binding domain known as the MADS-box. Members of this gene family display primarily floral-specific expression and are homologous to transcription factors found in several animal and fungal species. Molecular evolutionary analyses reveal that there are appreciable differences in the substitution rates between different domains of these plant MADS-box genes. Phylogenetic analyses also demonstrate that members of the plant MADS-box gene family are organized into several distinct gene groups: the AGAMOUS, APETALA3/PISTILLATA and APETALA1/AGL9 groups. The shared evolutionary history of members of a gene group appear to reflect the distinct functional roles these MADS-box genes play in flower development. Molecular evolutionary analyses also suggest that these different gene groups were established in a relatively short span of evolutionary time and that the various floral homeotic loci originated even before the appearance of the flowering plants.
Feedback activation of factor XI by thrombin does not occur in plasma (2007)

In this study, we tested the hypothesis that factor XI (FXI) activation occurs in plasma following activation of the extrinsic pathway by thrombin-mediated feedback activation. We used two different assays: (i) a direct measurement of activated FXI by ELISA and (ii) a functional assay that follows the activation of the coagulation cascade in the presence or absence of a FXI inhibiting antibody by monitoring thrombin activity. We failed to detect any FXI activation or functional contribution to the activation of the coagulation cascade in platelet poor or platelet-rich plasma, when activation was initiated by thrombin or tissue factor. Additionally, we found that, in the absence of a contact system inhibitor during blood draw, contact activation of FXI can mistakenly appear as thrombin- or tissue-factor-dependent activation. Thus, activation of FXI by thrombin in solution or on the surface of activated platelets does not appear to play a significant role in a plasma environment. These results call for reevaluation of the physiological role of the contact activation system in blood coagulation.
Programming parallel algorithms (1996)

In the past 20 years there has been treftlendous progress in developing and analyzing parallel algorithftls. Researchers have developed efficient parallel algorithms to solve most problems for which efficient sequential solutions are known. Although some of these algorithms are efficient only in a theoretical framework, many are quite efficient in practice or have key ideas that have been used in efficient implementations. This research on parallel algorithms has not only improved our general understanding ofparallelism but in several cases has led to improvements in sequential algorithms. Unf:ortunately there has been less success in developing good languages f:or prograftlftling parallel algorithftls,
Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. (1993)

A novel member of the serine/threonine protein kinase gene family, designated sgk, for serum and glucocorticoid-regulated kinase, was identified in a differential screen for glucocorticoid-inducible transcripts expressed in the Con8.hd6 rat mammary tumor cell line. sgk encodes a protein of 49 kDa which has significant sequence homology (45 to 55% identity) throughout its catalytic domain with rac protein kinase, the protein kinase C family, ribosomal protein S6 kinase, and cyclic AMP-dependent protein kinase. sgk mRNA is expressed in most adult rat tissues, with the highest levels in the thymus, ovary, and lung, as well as in several rodent and human cell lines. sgk mRNA was stimulated by glucocorticoids and by serum within 30 min, and both inductions were independent of de novo protein synthesis. The transcriptional regulation by glucocorticoids is a primary response, since the promoter of sgk contains a glucocorticoid response element consensus sequence 1.0 kb upstream of the start of transcription which is able to stimulate chloramphenicol acetyltransferase reporter gene activity in a dexamethasone-dependent manner. Antibodies that specifically recognize sgk-encoded protein on an immunoblot were generated. This protein was shown to increase in abundance with glucocorticoid treatment in a manner which paralleled the mRNA accumulation. This is the first report of a presumed serine/threonine protein kinase that is highly regulated at the transcriptional level by glucocorticoid hormones and suggests a novel interplay between glucocorticoid receptor signalling and a protein kinase of the second messenger family.
Inverted gate GaAs MESFET by epitaxial liftoff (1992)

A GaAs film deposited on metal by epitaxial liftoff can form a Schottky barrier. This film is used make a 1μm gate length inverted gate GaAs metal-semiconductor field-effect transistor (MESFET) that can be pinched off by the inverted gate.
Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to isolate long-term stem cells (2001)

Clonogenic multipotent mouse hematopoietic stem cells (HSCs) and progenitor cells are contained within the c-kit(+) (K) lineage(-/lo) (L) Sca-1(+) (S) population of hematopoietic cells; long-term (LT) and short-term (ST) HSCs are Thy-1.1(lo). c-kit is a member of the receptor tyrosine kinase family, a class of receptors that are important in the proliferation and differentiation of hematopoietic cells. To establish whether the Flk-2/Flt3 receptor tyrosine kinase was expressed on the most primitive LT-HSCs, we sorted highly purified multipotent stem and progenitor cells on the basis of Flk-2 surface expression and used them in competitive reconstitution assays. Low numbers of Flk-2(-) HSCs gave rise to long-term multilineage reconstitution in the majority of recipients, whereas the transfer of Flk-2(+) multipotent cells resulted in mostly short-term multilineage reconstitution. The KLS subset of adult mouse bone marrow was analyzed for Flk-2 and Thy-1.1 expression. Three phenotypically and functionally distinct populations were isolated: Thy(lo) Flk-2(-) (LT-HSCs), Thy(lo) Flk-2(+) (ST-HSCs), and Thy(-) Flk-2(+) multipotent progenitors. The loss of Thy-1.1 and gain of Flk-2 expression marks the loss of self-renewal in HSC maturation. The addition of Flk-2 antibody to the lineage mix allows direct isolation of LT-HSC from adult bone marrow as c-kit(+) lin(-) Sca-1(+) Flk-2(-) from many strains of mice. Fetal liver HSCs are contained within Flk-2(-) and Flk-2(+) KTLS cells.
Involvement of mTORC1 and mTORC2 in regulation of glioblastoma multiforme growth and motility (2009)

The AKT/mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in glioblastoma multiforme (GBM) oncogenesis due to activation of AKT. We studied two distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), through which mTOR controls cell survival, growth and motility. Inhibition of mTOR by rapamycin (RAPA) resulted in time-dependent suppression of S6 ribosomal protein (pS6KSer235/236; mTORC1 substrate) and caused transient suppression of pAKTSer473 (mTORC2 substrate) at 1 to 3 h followed by a consistent increase from 6 to 24 h. Inhibition of mTOR or phosphoinositide 3-kinase (PI3K) suppressed platelet-derived growth factor (PDGF)- or fibronectin (FN)-induced activation of p70S6KThr389. Combined inhibition of mTOR and PI3K abolished PDGF- or FN-induced activation of STAT3Ser727. Expression of pAKT was suppressed by siRNA silencing of mTORC2 co-protein rictor, but not by mTORC1 co-protein raptor. GBM cell proliferation and motility paralleled the activation of mTORC2. Combined inhibition of mTOR and PI3K had an additive effect on suppressing cell growth and motility. PDGF-induced nuclear localization of mTOR was blocked by pre-treatment with RAPA. The results demonstrated that an activation of mTORC2 occurs when mTORC1 is inhibited by RAPA. Therefore, simultaneous suppression of mTORC1 and mTORC2 may provide novel therapy for GBM.
Inhibition of transmitter release by botulinum neurotoxin A (1989)

1. The contribution of a proteolytic fragment (H2L) of botulinum neurotoxin type A (comprised of the aminoterminal region of the heavy-chain disulphide-linked to the light chain) to inhibition of neurotransmitter release was investigated, using central cholinergic synapses of Aplysia, rodent nerve-diaphragm preparations and cerebrocortical synaptosomes. 2. No reduction in neurotransmitter release was observed following external application to these preparations of highly purified H2L or after intracellular injection into Aplysia neurons. 3. The lack of activity was not the result of alteration in the light chain of H2L during preparation of the latter because (a) renaturation of this light chain with intact heavy chain produced a toxic di-chain form and (b) simultaneous application of heavy chain and light chain from H2L inhibited transmitter release in Aplysia. 4. Bath application of H2L and heavy chain together inhibited release of transmitter; however, at the neuromuscular junction the potency of this mixture was much lower than that of native toxin. A similar blockade resulted when heavy chain was applied intracellularly and H2L added to the bath, demonstrating that H2L is taken up into cholinergic neurons of Aplysia. This uptake is shown to be mediated by the amino-terminal moiety of heavy chain (H2), because bath application of light chain plus H2 led to a decrease in acetylcholine release from a neuron that had been injected with heavy chain. 5. A role within the neuron is implicated for a carboxy-terminal portion of heavy chain (H1) since intracellular injection of light chain and H2 did not affect transmitter release. Although the situation is unclear in mammalian nerves, these collective findings indicate that blockade of transmitter release in Aplysia neurons requires the intracellular presence of light chain and H1 (by inference), whilst H2 contributes to the internalization step.
Discovery of Orally Active Isofuranones as Potent, Selective Inhibitors of Hematopoetic Progenitor Kinase 1 (2021)

While the discovery of immune checkpoint inhibitors has led to robust, durable responses in a range of cancers, many patients do not respond to currently available therapeutics. Therefore, an urgent need exists to identify alternative mechanisms to augment the immune-mediated clearance of tumors. Hematopoetic progenitor kinase 1 (HPK1) is a serine-threonine kinase that acts as a negative regulator of T-cell receptor (TCR) signaling, to dampen the immune response. Herein we describe the structure-based discovery of isofuranones as inhibitors of HPK1. Optimization of the chemotype led to improvements in potency, selectivity, plasma protein binding, and metabolic stability, culminating in the identification of compound <b>24</b>. Oral administration of <b>24</b>, in combination with an anti-PD1 antibody, demonstrated robust enhancement of anti-PD1 efficacy in a syngeneic tumor model of colorectal cancer.
Standardization of Cardiac Troponin I Assays: Round Robin of Ten Candidate Reference Materials (2001)

The cRMs demonstrating the best performance characteristics in 13 cTnI analytical systems will be included in subsequent activities of the cTnI Standardization Committee of the AACC.
A signal-decomposed and interference-annihilated approach to hyperspectral target detection (2004)

A hyperspectral imaging sensor can reveal and uncover targets with very narrow diagnostic wavelengths. However, it comes at a price that it can also extract many unknown signal sources such as background and natural signatures as well as unwanted man-made objects, which cannot be identified visually or a priori. These unknown signal sources can be referred to as interferers, which generally play a more dominant role than noise in hyperspectral image analysis. Separating such interferers from signals and annihilating them subsequently prior to detection may be a more realistic approach. In many applications, the signals of interest can be further divided into desired signals for which we want to extract and undesired signals for which we want to eliminate to enhance signal detectability. This paper presents a signal-decomposed and interference-annihilated (SDIA) approach in applications of hyperspectral target detection. It treats interferers and undesired signals as separate signal sources that can be eliminated prior to target detection. In doing so, a signal-decomposed interference/noise (SDIN) model is suggested in this paper. With the proposed SDIN model, the orthogonal subspace projection-based model and the signal/background/noise model can be included as its special cases. As shown in the experiments, the SDIN model-based SDIA approach generally can improve the performance of the commonly used generalized-likelihood ratio test and constrained energy minimization approach on target detection and classification.
Multi-cue Zero-Shot Learning with Strong Supervision (2016)

Scaling up visual category recognition to large numbers of classes remains challenging. A promising research direction is zero-shot learning, which does not require any training data to recognize new classes, but rather relies on some form of auxiliary information describing the new classes. Ultimately, this may allow to use textbook knowledge that humans employ to learn about new classes by transferring knowledge from classes they know well. The most successful zero-shot learning approaches currently require a particular type of auxiliary information - namely attribute annotations performed by humans - that is not readily available for most classes. Our goal is to circumvent this bottleneck by substituting such annotations by extracting multiple pieces of information from multiple unstructured text sources readily available on the web. To compensate for the weaker form of auxiliary information, we incorporate stronger supervision in the form of semantic part annotations on the classes from which we transfer knowledge. We achieve our goal by a joint embedding framework that maps multiple text parts as well as multiple semantic parts into a common space. Our results consistently and significantly improve on the state-of-the-art in zero-short recognition and retrieval.