gebhart/patrepeval huggingface dataset:
The role of exogenous heart-RNA in development of the chick embryo cultivated in vitro. (1970)

The physiological effect of fresh calf heart-RNA was studied on the explanted chick blastoderm at the definitive streak stage. It was found that heart-RNA interferes with normal development of the central nervous system, especially forebrain, and of the body axis, but not with normal development of the heart. To analyse this effect further, the untreated and RNA-treated fragments of the antero-lateral blastoderm were investigated by intrablastodermal transplant and in vitro . Approximately 50% of the treated grafts transplanted intrablastodermally developed into heart, but none of the controls. In vitro formation of the heart-like structure was found in 45% of the heart-RNA-treated series as opposed to 20% of the PC saline controls and none of the liver-RNA series. When theexplants of the presumptive forebrain were treated with heart-RNA and cultured in isolation in vitro , 11% developed into brain vesicle compared with 76% of the controls. It appears, therefore, that heart-RNA has somehow collaborated with the macromolecules responsible for heart formation but interfered with those responsible for the development of the central nervous system.
NMR Structure of the α-Hemoglobin Stabilizing Protein (2004)

The structure of alpha-hemoglobin stabilizing protein (AHSP), a molecular chaperone for free alpha-hemoglobin, has been determined using NMR spectroscopy. The protein native state shows conformational heterogeneity attributable to the isomerization of the peptide bond preceding a conserved proline residue. The two equally populated cis and trans forms both adopt an elongated antiparallel three alpha-helix bundle fold but display major differences in the loop between the first two helices and at the C terminus of helix 3. Proline to alanine single point mutation of the residue Pro-30 prevents the cis/trans isomerization. The structure of the P30A mutant is similar to the structure of the trans form of AHSP in the loop 1 region. Both the wild-type AHSP and the P30A mutant bind to alpha-hemoglobin, and the wild-type conformational heterogeneity is quenched upon complex formation, suggesting that just one conformation is the active form. Changes in chemical shift observed upon complex formation identify a binding interface comprising the C terminus of helix 1, the loop 1, and the N terminus of helix 2, with the exposed residues Phe-47 and Tyr-51 being attractive targets for molecular recognition. The characteristics of this interface suggest that AHSP binds at the intradimer alpha1beta1 interface in tetrameric HbA.
A novel variant of human interferon alpha 1 gene. (1992)

A 520-base pair human IFN-alpha gene was isolated by PCR method twice from chromosome DNA of a Chinese (Han Nationality) fetal liver. The nucleotide sequences were determined. These two separately amplified DNA fragments shared the completely identical nucleotide sequence but possessed C and G at positions 410 and 541, respectively, which differ from those of IFN-alpha 1 and IFN-alpha D previously described. Therefore the deduced amino acid sequence would have an Ala at position 114 and a Val at position 158. At all other sites it has the same amino acids as those in IFN-alpha 1 and IFN-alpha D. We recommend that IFN-alpha D gene, IFN-alpha I gene and IFN-alpha I/158V gene found in our laboratory, be named IFN-alpha 1a gene, IFN-alpha 1b gene and IFN-alpha 1c gene.
Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines (2005)

The fate of tumor-specific CD4(+) T cells is central to the outcome of the host immune response to cancer. We show that tumor antigen recognition by a subset of CD4(+) T cells led to their differentiation into cells capable of suppressing naive and Th1 effector cells. Such tumor-induced regulatory T cells (TMTregs) arose both from precommitted "natural" regulatory T cells and CD4(+)CD25(-)GITR(low) precursors. Once induced, TMTregs were capable of maintaining suppressor activity long after transfer into antigen-free recipients. Suppression was mediated by GITR(high) cells residing within both CD25(+) and CD25(-) subsets. Vaccination of the tumor-bearing host concomitantly expanded TMTregs and effector cells, but suppression was dominant, blunting the expansion of naive tumor-specific T cells and blocking the execution of effector function in vitro and in vivo. These studies illustrate the possibility that therapeutic vaccination could actually worsen host tolerance to tumor antigens and support treatment paradigms that seek to not only increase the frequency of tumor-specific T cells, but to do so in conjunction with strategies that inactivate or remove regulatory T-cell populations.
Trichlorosilane induced cleavage. A mild method for retrieving carbinols from carbamates (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTrichlorosilane induced cleavage. A mild method for retrieving carbinols from carbamatesW. H. Pirkle and J. R. HauskeCite this: J. Org. Chem. 1977, 42, 16, 2781–2782Publication Date (Print):August 1, 1977Publication History Published online1 May 2002Published inissue 1 August 1977https://pubs.acs.org/doi/10.1021/jo00436a029https://doi.org/10.1021/jo00436a029research-articleACS PublicationsRequest reuse permissionsArticle Views476Altmetric-Citations58LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Molecular-Based Equations of State for Associating Fluids: A Review of SAFT and Related Approaches (2001)

We present a review of recent advances in the statistical associating fluid theory (SAFT). In contrast to the “chemical theory”, in which nonideality is explained in terms of chemical reactions between the species, SAFT and similar approaches relate nonideality to the intermolecular forces involved. Such physical theories can be tested against molecular simulations, and improvements to the theory can be made where needed. We describe the original SAFT approach and more recent modifications to it. Emphasis is placed on pointing out that SAFT is a general method and not a unique equation of state. Applications to a wide variety of fluids and mixtures are reviewed, including aqueous mixtures and electrolytes, liquid−liquid immiscible systems, amphiphilic systems, liquid crystals, polymers, petroleum fluids, and high-pressure phase equilibria.
Generation of Red Blood Cells from Human Induced Pluripotent Stem Cells (2011)

Differentiation of human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs) into the erythroid lineage of cells offers a novel opportunity to study erythroid development, regulation of globin switching, drug testing, and modeling of red blood cell (RBC) diseases in vitro. Here we describe an approach for the efficient generation of RBCs from hiPSC/hESCs using an OP9 coculture system to induce hematopoietic differentiation followed by selective expansion of erythroid cells in serum-free media with erythropoiesis-supporting cytokines. We showed that fibroblast-derived transgenic hiPSCs generated using lentivirus-based vectors and transgene-free hiPSCs generated using episomal vectors can be differentiated into RBCs with an efficiency similar to that of H1 hESCs. Erythroid cultures established with this approach consisted of an essentially pure population of CD235a(+)CD45(-) leukocyte-free RBCs with robust expansion potential and long life span (up to 90 days). Similar to hESCs, hiPSC-derived RBCs expressed predominately fetal γ and embryonic ɛ globins, indicating complete reprogramming of β-globin locus following transition of fibroblasts to the pluripotent state. Although β-globin expression was detected in hiPSC/hESC-derived erythroid cells, its expression was substantially lower than the embryonic and fetal globins. Overall, these results demonstrate the feasibility of large-scale production of erythroid cells from fibroblast-derived hiPSCs, as has been described for hESCs. Since RBCs generated from transgene-free hiPSCs lack genomic integration and background expression of reprogramming genes, they would be a preferable cell source for modeling of diseases and for gene function studies.
Inhibition of Cell Proliferation and AP-1 Activity by Acrolein in Human A549 Lung Adenocarcinoma Cells Due to Thiol Imbalance and Covalent Modifications (2002)

Acrolein, a reactive alpha,beta-unsaturated aldehyde, is a common environmental pollutant, a metabolite of the anticancer drug cyclophosphamide, and a byproduct of lipid peroxidation. An increase in acrolein production has been proposed as a marker for Alzheimer's disease, diabetic glomerular lesions, and atherosclerosis. Acrolein is a potent inhibitor of cell proliferation at nonlethal doses and may act through effects on redox-regulated transcription factors. We previously reported that NF-kappaB activation is inhibited by acrolein in the A549 lung adenocarcinoma cell line in an IkappaB-independent manner [Horton et al. (1999) J. Biol. Chem. 274, 9200-9206]. The current data demonstrate that AP-1 activation in A549 cells is decreased by 26 and 50% at 0.5 and 1 h, respectively, after exposure to 50 fmol/cell (a nonlethal dose) of acrolein. Inhibition of AP-1 activation also occurred following treatment with buthionine sulfoximine to deplete glutathione to the same extent as seen with acrolein. c-jun antisense treatments depressed c-jun protein below detectable levels at 4 h and inhibited cell proliferation (as assessed by [(3)H]thymidine incorporation) by 80%. Immunoprecipitation of c-jun protein after treating A549 cells with acrolein revealed the presence of a lysine-acrolein adduct. There was, however, no effect of acrolein on c-jun N-terminal kinase activity or c-jun phosphorylation. These data indicate that the inhibition of cell proliferation induced by acrolein correlates with the depletion of glutathione as well as the inhibition of AP-1 activation. AP-1 activation is likely affected both through changes in cellular thiol redox balance and by covalent modification of acrolein to c-jun, but not through effects on c-jun phosphorylation.
Attuning notification design to user goals and attention costs (2003)

Why is the attentive user interface paradigm important for human-computer interaction? The human attention system is so sensitive to various methods of notification that traditional design involves too much compromise and guesswork.
Corpus Luteum Regression Induced by Prostaglandin F2α1 (1970)

SINCE the original observation by Loeb (11) that hysterectomy of the guinea pig during the luteal phase caused maintenance of the corpora lutea, a valid physiological mechanism has been sought to explain this phenomenon, which has been recorded in a number of other species (see review 1). Pharris and Wyngarden (18) proposed that since prostaglandin F2α (PGF2α) is an abundant uterine prostaglandin (19) and since it has a pronounced venoconstricting effect (5), it is potentially a substance which might control luteal regression. They reported that PGF2α administered subcutaneously to rats at 1 mg/kg/day caused a dramatic shortening of pseudopregnancy (18). A similar effect was observed in the pseudopregnant hysterectomized hamster (8) and in the hysterectomized guinea pig (3). This paper reports the effect on ovarian blood flow and progesterone secretion rate of infusing PGF2α into the sheep ovary autotransplanted with vascular anastomoses to the vessels of the neck (7).
Apoptosis in cancer (2000)

In the last decade, basic cancer research has produced remarkable advances in our understanding of cancer biology and cancer genetics. Among the most important of these advances is the realization that apoptosis and the genes that control it have a profound effect on the malignant phenotype. For example, it is now clear that some oncogenic mutations disrupt apoptosis, leading to tumor initiation, progression or metastasis. Conversely, compelling evidence indicates that other oncogenic changes promote apoptosis, thereby producing selective pressure to override apoptosis during multistage carcinogenesis. Finally, it is now well documented that most cytotoxic anticancer agents induce apoptosis, raising the intriguing possibility that defects in apoptotic programs contribute to treatment failure. Because the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity, apoptosis provides a conceptual framework to link cancer genetics with cancer therapy. An intense research effort is uncovering the underlying mechanisms of apoptosis such that, in the next decade, one envisions that this information will produce new strategies to exploit apoptosis for therapeutic benefit.
A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. (2013)

3000 Background: Tumor PD-L1 mediates cancer immune evasion. Therefore, inhibition of PD-L1 binding represents an attractive strategy to restore tumor-specific T-cell immunity.MPDL3280A, a human monoclonal antibody containing an engineered Fc-domain designed to optimize efficacy and safety, targets PD-L1, blocking PD-L1 from binding its receptors, including PD-1 and B7.1. Methods: A study was conducted with MPDL3280A administered IV q3w in pts with locally advanced or metastatic solid tumors, including 3+3 dose-escalation and expansion cohorts. ORR was assessed by RECIST v1.1 and includes u/cCR and u/cPR. Results: As of Jan 10, 2013, 171 pts were evaluable for safety. Administered doses include ≤1 (n=9), 3 (n=3), 10 (n=35), 15 (n=57) and 20 mg/kg (n=67). Pts in the dose-escalation cohorts did not experience DLTs. No MTD was identified. Pts had received MPDL3280A for a median duration of 127 days (range 1-330). 39% of pts reported G3/4 AEs, regardless of attribution. AEs of special interest included hepatitis, rash and colitis. No G3-5 pneumonitis was observed. MPDL3280A PK was linear at doses ≥1 mg/kg. 122 pts enrolled prior to Jul 1, 2012 were evaluable for efficacy. RECIST responses were observed in multiple tumor types including NSCLC, RCC, melanoma, CRC and gastric cancer. An ORR of 21% (25/122) was observed in nonselected solid tumors, including several pts who demonstrated tumor shrinkage within days of initiating treatment. Additional pts had delayed responses after apparent radiographic progression (not included in the ORR). Some responders demonstrated prolonged SD prior to RECIST responses. The 24-week PFS was 44%. Pts with PD-L1–positive tumors (from archival samples) showed an ORR of 39% (13/33) and a PD rate of 12% (4/33). In contrast, patients with PD-L1–negative tumors showed an ORR of 13% (8/61) and a PD rate of 59% (36/61). As of the cutoff date, all responses are ongoing or improving. Updated data will be presented. Conclusions: MPDL3280A was well tolerated, with no pneumonitis-related deaths. Durable responses were observed in a variety of tumors. PD-L1 tumor status appears to correlate with responses to MPDL3280A. PK supports q3w dosing at 15 mg/kg or fixed-dose equivalent. Clinical trial information: NCT01375842.
Copper(I) Bromide/N-(n-Octyl)-2-pyridylmethanimine−Mediated Living-Radical Polymerization of Methyl Methacrylate Using Carbosilane Dendritic Initiators (2000)

The zeroth (Si{(CH2)3SiMe2(C6H4CH2OC(O)CMe2Br)}4), 2, and first (Si{(CH2)3Si((CH2)3SiMe2(C6H4CH2OC(O)CMe2Br))3}4), 3, generation of 2-bromoisobutyryl functionalized carbosilane dendrimers have been successfully applied as initiators for the copper(I) bromide/N-(n-octyl)-2-pyridylmethanimine-mediated living-radical polymerization of methyl methacrylate. The overall rate of polymerization are comparable for the two dendritic initiators studied, 2 (3.4 × 10-5 mol L-1 s-1) and 3 (4.8 × 10-5 mol L-1 s-1) with the benzylic model compound C6H5CH2OC(O)CMe2Br (1) showing a lower rate of polymerization for both dendritic initiators, (7.3 × 10-5 mol L-1 s-1) where [initiator sites] = 1.87 × 10-2 mol L-1. We postulate that this is caused by initial intramolecular termination. The molecular weight distribution is less than 1.3 after 3 h reaction time. Initiator 3, however, produces star−star coupling throughout the polymerization. When the dendritic periphery is partialy functionalized (statistically two and six arms of the first generation dendrimer, respectively, 4 and 5) the control of the molecular weight distribution was lost (PDI > 3) for 4 as a result of too low of a value for [initiator site], i.e., 3.12 × 10-3 mol L-1.
Degradable, Thermo-Sensitive Poly(N-isopropyl acrylamide)-Based Scaffolds with Controlled Porosity for Tissue Engineering Applications (2010)

We have developed a thermoresponsive poly(N-isopropyl acrylamide)-based scaffold with degradability and controlled porosity. Biodegradable poly(N-isopropyl acrylamide) hydrogels were synthesized by photocopolymerization of N-isopropylacrylamide with 2-methylene-1,3-dioxepane and polycaprolactone dimethacrylate. The hydrogels' phase transition temperature, swelling, and viscoelastic properties, as well as hydrolytic degradability at 25 and 37 °C, were explored. A sphere-templating technique was applied to fabricate hydrogel scaffolds with controllable pore size and a highly interconnected porous structure. The scaffold pore diameter change as a function of temperature was evaluated and, as expected, pores decreased in diameter when the temperature was raised to 37 °C. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test results suggested neither the scaffolds nor their degradation products were cytotoxic to NIH3T3 cells. Scaffolds with 55 ± 5 μm pore diameter were loaded with NIH3T3 cells and then were warmed to 37 °C entrapping cells in pores approximately 39 μm in diameter, a size range we have found to be optimal for angiogenesis and biointegration. Cells showed uniform infiltration and an elongated morphology after 7 days of culture. Due to the controlled monodisperse pore diameter, highly interconnected architecture, fully degradable chemistry and thermoresponsive properties, the polyNIPAM-based scaffolds developed here are attractive for applications in tissue engineering.
Enantio-DNA recognizes complementary RNA but not complementary DNA (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantio-DNA recognizes complementary RNA but not complementary DNAShizuyoshi Fujimori, Koichi Shudo, and Yuichi HashimotoCite this: J. Am. Chem. Soc. 1990, 112, 20, 7436–7438Publication Date (Print):September 1, 1990Publication History Published online1 May 2002Published inissue 1 September 1990https://pubs.acs.org/doi/10.1021/ja00176a077https://doi.org/10.1021/ja00176a077research-articleACS PublicationsRequest reuse permissionsArticle Views194Altmetric-Citations57LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The association between real-world CA19-9 level monitoring patterns and with clinical outcomes among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in the second- and third-line of therapy. (2021)

e16251 Background: Pancreatic cancer has an aggressive disease course, mandating close clinical monitoring while on treatment. Evaluation of treatment response in patients with mPDAC necessitates scheduled clinical and radiographic assessments along with monitoring serum CA 19-9 levels. We investigated the impact of serum CA 19-9 monitoring and its association with clinical outcomes in patients with mPDAC who received second- (2L) and third line (3L) in a population-based setting. Methods: Data were extracted from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database for patients diagnosed with mPDAC and subsequently treated in the 2L or 3L setting between January 1, 2014 and June 30, 2020. Serum CA 19-9 levels at baseline were extracted – defined as the values obtained ≤ 60 days of treatment initiation and during treatment. CA 19-9 levels &gt; 40 IU/mL were considered elevated. Survival analysis was performed using Kaplan-Meier methods. Categorical measures were compared with a chi-square test and survival outcomes with a log-rank test. Results: There were 2,402 patients who received 2L and 790 patients who received 3L treatment included in the study. Among the 2L cohort, median age at treatment initiation was 67 years (IQR: 60 – 73), 54% were male, 57% had an ECOG score of 0-1, and 82% had a baseline serum CA 19-9 level available. Among the 3L cohort, median age at treatment initiation was 67 years (IQR: 60 – 73), 53% were male, 58% had an ECOG score of 0-1, and 84% had a baseline CA 19-9 level available. Most patients in the 2L and 3L cohorts had an elevated CA 19-9 at baseline, 85.2% and 82.0%, respectively. Among the 2L and 3L cohorts, 38.5% and 31.9% had CA 19-9 levels decrease/remain stable during treatment and 27.6% and 31.4% had levels increase during treatment, respectively. Patients with normal baseline CA 19-9 experienced longer survival than patients with elevated levels [2L: 7.2 months (95% CI: 6.1 – 9.2) vs 5.2 months (4.9 – 5.6), p &lt; 0.001; 3L: 6.1 months (5.4 – 9.1) vs 3.9 months (3.4 – 4.3), p &lt; 0.001]. Similarly, patients with decreasing/stable CA 19-9 during treatment had longer survival than patients who had their CA 19-9 levels increase [2L: 8.2 months (7.7 – 8.5) vs 4.3 months (4.1 – 4.7), p &lt; 0.001; 3L: 7.5 months (6.6 – 9.2) vs 3.7 months (3.4 – 4.3), p &lt; 0.001]. Conclusions: In this large, contemporary, real-world study of patients with mPDAC, CA 19-9 levels at treatment initiation had a prognostic value across later lines of therapy. Routine serial monitoring of CA 19-9 levels during treatment, in addition to clinical and radiographic assessment, may help with timely additional diagnostic testing and treatment intervention. Further validation studies are needed to understand the generalizability of these results.
In vivo genome editing via CRISPR-Cas9 mediated homology-independent targeted integration (2016)

A method for CRISPR-based genome editing that harnesses cellular non-homologous end joining activity to achieve targeted DNA knock-in in non-dividing tissues.