gebhart/patrepeval huggingface dataset:
Generation of transducible versions of transcription factors Oct4 and Sox2 (2008)

The transcription factors Oct4 and Sox2 are two of the main regulators of pluripotency in embryonic stem cells. Since the importance of non-genetic modification is continually increasing, particularly for therapeutic application of manipulated cells, the aim of the present study was to generate cell-permeant Oct4 and Sox2 proteins for the direct cellular delivery of active proteins. Protein transduction allowing cellular manipulation to circumvent genetic modification of target cells has recently been developed. We present a new expression vector system, pSESAME, that facilitates the generation of transducible proteins. Using pSESAME, both Oct4 and Sox2 were genetically fused with a TAT protein transduction domain that promotes cellular penetration. The recombinant purified Oct4 and Sox2 fusion proteins display DNA-binding properties comparable to their endogenous counterparts, and exhibit cellular entry and the ability to modulate the transcriptional machinery maintaining pluripotency of mouse embryonic stem cells. In a rescue assay we demonstrate that transducible Oct4 and Sox2 fusion proteins can compensate knockdown of Pou5f1 and Sox2, respectively. This study provides powerful tools for the modulation of stem cell properties without genetic interference.
A General Procedure for the Esterification of Carboxylic Acids with Diazoalkanes Generated in Situ by the Oxidation of N-tert-Butyldimethylsilylhydrazones with (Difluoroiodo)benzene (2004)

The bimolecular reaction of carboxylic acids with diazoalkanes to form esters is among the mildest and most efficient of organic transformations but is seldom used in synthesis beyond the important case of methyl esterification. This is largely a consequence of the inaccessibility and poor stability of higher diazoalkanes as substrates. In this work we describe a new method for the synthesis of diazoalkanes by the oxidation of N-tert-butyldimethylsilylhydrazones (TBSHs) with (difluoroiodo)benzene, a reagent heretofore unexplored in the context of hydrazone oxidation. When conducted in the presence of a carboxylic acid substrate, the oxidation leads to efficient esterification in situ. In addition to greatly extending the range of diazoalkanes that are now available for esterifications, this new protocol offers significant advantages with regard to safety, for diazo intermediates are neither isolated nor achieve appreciable concentrations during the reaction.
Negative modultors of excitatory amino acids in episodic and chronic migraine: preventing and reverting chronic migraine. Special lecture 7th INWIN Congress. (1998)

The mechanism capable of transforming episodic migraine into chronic migraine is attributed by the authors to hyperalgesia and related neuroplastic changes, chiefly long-term potentiation, due to the action of excitatory amino acids, chiefly the ones acting at N-methyl D-aspartate (NMDA) receptor. A preeminent role has been attributed to 'third hyperalgesia', a newly observed type of hyperalgesia which is inheritable and can act as a ground for the above-mentioned mechanism of 'chronicization' of migraine. The role of primary and secondary hyperalgesia in giving redundance to neuraxial abnormalities is also discussed. The fact that NMDA noncompetitive antagonist ketamine and gabapentin, inhibitor of the neuronal synthesis of L-glutamate, can cure chronic migraine, so far considered refractory to prophylactic therapies, gives indirect but evident support to the mechanism suggested above. The antinociceptive role of the above-mentioned negative modulators of excitatory amino acids and the possible interplay between ionotropic and metabotropic receptors are also taken into consideration.
Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C (2004)

Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C-labeled compound bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated. The MTT was determined to be 2.8 +/- 0.8 sec. However, arterial partial-volume effects in the animal model prevented accurate absolute quantification of CBF and CBV. It was demonstrated that depolarization of the hyperpolarized 13C tracer via relaxation and the imaging sequence had little influence on CBF assessment when the time resolution of the imaging sequence was short compared to the MTT. However, CBV and MTT were increasingly underestimated as MTT or the depolarization rate increased if depolarization was not taken into account. With a modified bolus-tracking theory depolarization could be compensated for, assuming that the depolarization rate was known. Three separate compensation methods were investigated experimentally and by numerical simulations.
Cell therapy. (1998)

Cell therapy has emerged as a strategy for the treatment of many human diseases. Because no single cell or universal donor is likely to be useful for all diseases, it is the source and the desired function of the cell that will dictate which cell type is most useful for each disease. Concerns related to immunological compatibility, ability to multiply cells in vitro before transplantation and general issues of quality control and safety are now being addressed by the convergence of disciplines interested in the potential for cell therapy.
A Member of the Frizzled Protein Family Mediating Axis Induction by Wnt-5A (1997)

In Xenopus laevis embryos, the Wingless/Wnt-1 subclass of Wnt molecules induces axis duplication, whereas the Wnt-5A subclass does not. This difference could be explained by distinct signal transduction pathways or by a lack of one or more Wnt-5A receptors during axis formation. Wnt-5A induced axis duplication and an ectopic Spemann organizer in the presence of hFz5, a member of the Frizzled family of seven-transmembrane receptors. Wnt-5A/hFz5 signaling was antagonized by glycogen synthase kinase-3 and by the amino-terminal ectodomain of hFz5. These results identify hFz5 as a receptor for Wnt-5A.
Cellular Uptake of Oligodeoxyribonucleoside Methylphosphonates (1995)

The cellular uptake of oligodeoxyribonucleoside methylphosphonates has been evaluated using three radiolabeled oligomers. Oligomers I and II ([3H]-T8 and [3H]-T16, respectively) are nonionic methylphosphonate oligomers labeled with tritium on the phosphonate internucleotide linkage. EDA-III contains a single phosphodiester linkage, a [32P]-label and an ethylenediamine conjugate at the [32P]-5'-end. All three oligomers are stable in cells. At a 1 microM concentration, oligomer I is not taken up by human erythrocytes. The octanol/DPBS partition coefficients for oligomers I and II (1.5 x 10(-4) and 4.2 x 10(-4), respectively) further indicate that these molecules should not diffuse across cell membranes at appreciable rates. Oligomer I is taken up by HL-60 cells, although at a slower rate than the uptake of the fluid-phase marker sucrose. The cell-associated levels of oligomer II in K-562 cells following incubation of cells with the oligomer for 2 days is independent of concentration and nonsaturable, suggesting a mechanism of uptake independent of receptor. Finally, the initial uptake rate of EDA-III in mouse L cells is greater than the uptake of two oligodeoxyribonucleotides (T8, T16), reaching a plateau after 3 hours incubation with cells. These observations should aid in the elucidation of the mechanism by which this class of antisense agents enters the intracellular environment.
Minimal model estimation of glucose absorption and insulin sensitivity from oral test: validation with a tracer method (2004)

Measuring insulin sensitivity during the physiological milieu of oral glucose perturbation, e.g., a meal or an oral glucose tolerance test, would be extremely valuable but difficult since the rate of appearance of absorbed glucose is unknown. The reference method is a tracer two-step one: first, the rate of appearance of glucose (R(a meal)(ref)) is reconstructed by employing the tracer-to-tracee ratio clamp technique with two tracers and a model of non-steady-state glucose kinetics; next, this R(a meal)(ref) is used as the known input of a model describing insulin action on glucose kinetics to estimate insulin sensitivity (SI(ref)). Recently, a nontracer method based on the oral minimal model (OMM) has been proposed to estimate simultaneously the above quantities, denoted R(a meal) and SI, respectively, from plasma glucose and insulin concentrations measured after an oral glucose perturbation. This last method has obvious advantages over the tracer method, but its domain of validity has never been assessed against a reference method. It is thus important to establish whether or not the "nontracer" R(a meal) and SI compare well with the "tracer" R(a meal)(ref) and SI(ref). We do this comparison on a database of 88 subjects, and it is very satisfactory: R(a meal) profiles agree well with the R(a meal)(ref) and correlation of SI(ref) with SI is r = 0.86 (P < 0.0001). We conclude that OMM candidates as a reliable tool to measure both the rate of glucose absorption and insulin sensitivity from oral glucose tests without employing tracers.
Identifying Actionable Messages on Social Media (2015)

Text actionability detection is the problem of classifying user authored natural language text, according to whether it can be acted upon by a responding agent. In this paper, we propose a supervised learning framework for domain-aware, large-scale actionability classification of social media messages. We derive lexicons, perform an in-depth analysis for over 25 text based features, and explore strategies to handle domains that have limited training data. We apply these methods to over 46 million messages spanning 75 companies and 35 languages, from both Facebook and Twitter. The models achieve an aggregate population-weighted F measure of 0.78 and accuracy of 0.74, with values of over 0.9 in some cases.
Four Generations of Pyrrolopyrimidines (2002)

The pyrrolopyrimidines have been under study for several years at Pharmacia Corporation for a variety of potential therapeutic applications. This class of compound is typified by PNU-142731A (24a) and contains a tricylic, generally fully aromatic nucleus, to which are appended two pyrrolidine moieties and a heterocyclic-containing side chain. This paper will present the process development aspects of the synthesis of four candidates in the series, and the application of lessons learned as the clinical program continued to evolve.
Differential expression of bcl-2 and susceptibility to anti-Fas- mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils (1994)

The recently identified Fas antigen (Ag) is a cell surface molecule that can mediate apoptosis. The cytoplasmic product of proto-oncogene bcl-2 has been shown to prolong the cellular survival by inhibiting apoptosis. To elucidate the physiologic significance of expression of both molecules, we examined the expression of Fas Ag and bcl-2 on blood leukocyte populations and evaluated their sensitivity to the cytolytic action of anti-Fas antibody. Although Fas Ag was expressed on a fraction of lymphocytes, both neutrophils and monocytes expressed Fas Ag constitutively. In contrast, there was marked difference among these leukocytes regarding bcl-2 expression. Lymphocytes expressed bcl-2 intensely, but monocytes showed weaker bcl-2 expression, and neutrophils were essentially absent for bcl-2 expression. Seemingly reflecting this lack of bcl-2-expression, neutrophils more easily underwent apoptotic cell death in vitro as compared with monocytes and lymphocytes. We showed that anti-Fas antibody affectively accelerated apoptotic cell death in neutrophils. However, the apoptosis-inducing effect of anti-Fas antibody was minimal on monocytes, and lymphocytes were resistant to this antibody. These results suggest that anti-Fas-mediated cell death may, in part, be determined by bcl-2 expression status in Fas+ lymphoid and hematopoietic cells.
Stimulation of fibroblast collagen and total protein formation by an endothelial cell-derived factor. (1991)

We investigated the effect of medium conditioned by bovine aortic endothelial cells on collagen accumulation and total protein formation by human embryonic fibroblasts or bovine smooth muscle cells in cultures. The conditioned medium at a 1:10 dilution induced a twofold increase in collagen and total protein accumulation in fibroblast cultures. At low concentration (1:50 dilution), the conditioned medium stimulated collagen accumulation preferentially; at high concentration (1:10 dilution), overall protein synthesis also was increased. The increase in type I collagen accumulation was associated with an increase in the steady-state level of alpha 1 (I) mRNA for collagen. The conditioned medium increased the production of types I and III collagen without affecting the proportion of collagen types in both fibroblast and smooth muscle cell cultures. Partial purification of the endothelial cell-derived factor disclosed it to be a heat-stable protein with an apparent molecular weight of 8-10 kDa. The stimulation of protein formation by this substance was not inhibited by antibodies against transforming growth factor-beta or the insulinlike growth factor I receptor. The partially purified factor stimulated protein production without affecting fibroblast proliferation. This endothelial cell-derived protein may play a role in the remodeling of vascular connective tissue by stimulating collagen synthesis.
Comparison of Growth Factor and Platelet Concentration From Commercial Platelet-Rich Plasma Separation Systems (2010)

Products from commercially available PRP separation systems produce differing concentrations of growth factors and WBCs. Further research is necessary to determine the clinical relevance of these findings.
Biodehalogenation. Epoxidation of halohydrins, epoxide opening, and transhalogenation by a Flavobacterium species (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiodehalogenation. Epoxidation of halohydrins, epoxide opening, and transhalogenation by a Flavobacterium speciesC. E. Castro and E. W. BartnickiCite this: Biochemistry 1968, 7, 9, 3213–3218Publication Date (Print):September 1, 1968Publication History Published online1 May 2002Published inissue 1 September 1968https://doi.org/10.1021/bi00849a025RIGHTS & PERMISSIONSArticle Views267Altmetric-Citations68LEARN 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 InReddit PDF (541 KB) Get e-Alerts Get e-Alerts
Abstract LB-221: Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates (ADCs) demonstrate tumor specificity, unique sequence homology and in vitro and in vivo antitumor efficacy (2016)

Abstract Siamab Therapeutics is developing monoclonal antibodies and antibody drug conjugates (ADCs) targeting tumor-associated carbohydrate antigens such as Sialyl-Tn (STn). These antibodies are selected using a proprietary glycan microarray that enriches for candidates whose binding is protein independent, highly specific and demonstrates exceptional target affinity. STn is a cancer specific antigen that is expressed on the surface of carcinomas including ovarian, colon, prostate, and pancreatic tumors but is rarely present in normal tissue. STn expression has been linked to innate immune suppression, a chemoresistant phenotype, metastasis, and poor prognosis. Previous attempts to target this antigen in the clinic with synthetic glycan vaccines proved safe but lacked efficacy. Siamab has developed over 20 murine mAbs that bind STn with high affinity and specificity. When formatted as ADCs, anti-STn mAb-ADCs target and selectively kill STn expressing cells and also demonstrate efficacy in multiple xenograft studies. Multiple murine mAbs perform well in IHC studies with multiple solid tumor samples and tissue microarrays and demonstrate high tumor specificity. Remarkable sequence homology across all murine mAbs was observed in both heavy and light chains, and hot spots for hypermutation were identified. Humanization was successfully completed using a selection of mAbs and multiple humanized mAbs maintain their target specific binding, affinity and cytotoxicity in vitro. Our data demonstrates that high-affinity, STn-specific mAbs show promise both as therapies for solid tumors and as a potential tool for the development of biomarkers and companion diagnostics enabling selection of patients most likely to respond to therapy. Citation Format: David Eaverone, Jeff Behrens, Jillian Prendergast. Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates (ADCs) demonstrate tumor specificity, unique sequence homology and in vitro and in vivo antitumor efficacy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-221.
Phenotypic correction of Fanconi anemia in human hematopoietic cells with a recombinant adeno-associated virus vector. (1994)

Fanconi anemia (FA) is a recessive inherited disease characterized by defective DNA repair. FA cells are hypersensitive to DNA cross-linking agents that cause chromosomal instability and cell death. FA is manifested clinically by progressive pancytopenia, variable physical anomalies, and predisposition to malignancy. Four complementation groups have been identified, termed A, B, C, and D. The gene for the FA complementation group C, FACC, has been cloned. Expression of the FACC cDNA corrects the phenotypic defect of FA(C) cells, resulting in normalized cell growth in the presence of DNA cross-linking agents such as mitomycin C (MMC). Gene transfer of the FACC gene should provide a survival advantage to transduced hematopoietic cells, suggesting that FA might be an ideal candidate for gene therapy. We demonstrated efficient transduction, expression, and phenotypic correction in lymphoblastoid cell lines derived from FA (C) patients using a recombinant adeno-associated virus (rAAV) vector containing the FACC gene. Molecular characterization of the transduced FACC gene showed an intact unrearranged proviral genome with expression sufficient to normalize cell growth, cell cycle kinetics and chromosomal breakage in the presence of MMC. These observations were extended by testing rAAV transduction in hematopoietic progenitor cells. Peripheral blood CD34+ cells isolated from a FA (C) patient and transduced with rAAV/FACC virus yielded 5-10-fold more progenitor colonies than mock-infected cells, consistent with genetic "rescue" of corrected cells. This is the first demonstration of rAAV gene correction in primary human hematopoietic progenitor cells and has important implications for gene therapy of hematopoietic disorders, specifically FA.
Zinc Finger Recombinases with Adaptable DNA Sequence Specificity (2011)

Site-specific recombinases have become essential tools in genetics and molecular biology for the precise excision or integration of DNA sequences. However, their utility is currently limited to circumstances where the sites recognized by the recombinase enzyme have been introduced into the DNA being manipulated, or natural 'pseudosites' are already present. Many new applications would become feasible if recombinase activity could be targeted to chosen sequences in natural genomic DNA. Here we demonstrate efficient site-specific recombination at several sequences taken from a 1.9 kilobasepair locus of biotechnological interest (in the bovine β-casein gene), mediated by zinc finger recombinases (ZFRs), chimaeric enzymes with linked zinc finger (DNA recognition) and recombinase (catalytic) domains. In the "Z-sites" tested here, 22 bp casein gene sequences are flanked by 9 bp motifs recognized by zinc finger domains. Asymmetric Z-sites were recombined by the concomitant action of two ZFRs with different zinc finger DNA-binding specificities, and could be recombined with a heterologous site in the presence of a third recombinase. Our results show that engineered ZFRs may be designed to promote site-specific recombination at many natural DNA sequences.
Directional illumination analysis using beamlet decomposition and propagation (2006)

Abstract We evaluate directional illumination (DI) and acquisition-aperture efficacy through wave theory-based beamlet decomposition of the wavefield. Beamlet decomposition (wavelet transform along spatial axis) provides localizations in both space and direction of a wavefield. We introduce the image conditions in beamlet domain and local angle domain and then define the local image matrix (LIM). We calculate the DI in the image space for a given source or a group of sources by decomposing Green's functions into local angle domain at image points. Acquisition-aperture efficacy (AAE) matrix and acquisition dip-response (ADR) vector can be defined to quantify the efficacy of an acquisition configuration for a given subsurface point. As numerical examples, we calculate the DI maps and ADR maps for high- and low-velocity lens models and for the SEG-EAGE 2D salt model. We further investigate the influences of acquisition geometry and overlaying structures on the quality of prestack depth migration image for the subsalt area of the SEG-EAGE model. We find that the ADR maps for different dip angles have good correlation with the image qualities of the corresponding reflectors. DI analysis can be used in the aperture correction for image amplitude in local angle domain for wave theory-based migration methods.