gebhart/patrepeval huggingface dataset:
Tricontinuous Double Gyroid Cubic Phase in Triblock Copolymers of the ABA Type (1997)

We report the synthesis and morphological characterization of two triblock copolymers of the ABA type, where A is polystyrene (PS) and B polyisoprene (PI). The volume fraction of the minority component, PS or PI, is approximately 1/3. Cubic microdomain morphologies, already found in diblock and star block copolymers with the same composition range, are observed for the first time in the case of linear triblock copolymers. The two ABA triblocks are on opposite sides of the phase diagram, which signifies that both the A end blocks and the B midblock are capable of forming the interconnected double network structure. Investigation of the morphology was done via birefringence, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). Birefringence measurements showed each triblock structure to have isotropic optical properties. The characteristic ratio of the observed Bragg peaks, q2/q1, was approximately / for each sample, indicating a set of eight possible cubic space groups. TEM data showed an interconnected tricontinuous microdomain structure. Since the two triblocks have essentially complementary structures (PS = 0.32 in one and PI = 0.36 in the other), the TEM images of OsO4-stained thin sections are complementary and the diffraction patterns of the images are approximately equal according to Babinet's principle. Examination of high-symmetry projections demonstrated p6mm, p4mm, and c2mm symmetry present in the TEM images. Comparison with the 〈111〉, 〈100〉, and 〈110〉 projections of the eight cubic space groups satisfying the SAXS data eliminated all but the Fm3̄m and Ia3̄d groups as possible structures. Due to the observed connectivity of the structure, the Fm3̄m structure could be eliminated by inspection of possible network structures and the resultant symmetries. Computer simulations of a model structure (double gyroid) based on level surfaces with Ia3̄d symmetry and their Fourier transforms showed excellent agreement with the high-symmetry projections and their respective optical transforms.
Mutant IDH (mIDH) inhibitors, ivosidenib or enasidenib, with azacitidine (AZA) in patients with acute myeloid leukemia (AML). (2018)

7042 Background: Ivosidenib (IVO; AG-120) and enasidenib (ENA; AG-221) are oral inhibitors of mIDH1 and mIDH2 proteins. In vitro, mIDH inhibitor + AZA combinations enhance cell differentiation and apoptosis. We report results of an ongoing phase 1b/2 study of mIDH inhibitors + AZA in patients (pts) with newly diagnosed (ND) AML (NCT02677922). Methods: Adult pts with mIDH ND-AML ineligible for intensive treatment (Tx) receive continuous IVO (mIDH1) 500 mg or ENA (mIDH2) 100 or 200 mg QD, plus SC AZA 75 mg/m2 x 7d, in repeated 28d cycles. Response is defined by IWG 2003 AML criteria. Results: At data cutoff (Sep 1, 2017) 17 pts had received IVO 500 mg (n = 11) or ENA 100 mg (3) or 200 mg (3) + AZA in the phase 1b portion of the study; 11 were ongoing. IVO: Median age was 76 yrs. Median number of Tx cycles was 3 (range 1-13).Three pts discontinued Tx, 2 due to progressive disease (PD).AEs in ≥4 pts (any grade) were nausea (n = 8), constipation (6), fatigue (5) and diarrhea (4). Grade 3-4 hematological AEs (Table) occurred at similar frequency to what has been reported for AZA alone. Serious AEs in > 1 pt were pneumonia, febrile neutropenia (n = 2 each). Eight of 11 pts responded, including 4 complete remissions (CRs). ENA:Median age was 68 yrs. Median number of Tx cycles was 9 (1-13). Three pts discontinued Tx, 2 due to PD. Most common AEs (any grade) were nausea and hyperbilirubinemia (n = 4 each). Serious AEs in > 1 pt were pyrexia, bilirubin increase, pneumonia (n = 2 each). Four of 6 pts responded, including 2 CRs. Conclusions: mIDH inhibitor + AZA regimens were generally well tolerated in pts with ND-AML. Most AEs were grade 1-2 GI events and ENA-related indirect bilirubin elevations due to off-target UGT1A1 inhibition. Response rates are encouraging. Phase 1b enrollment completed in late 2017; updated data for all 23 IVO and 6 ENA pts will be presented, as well as longitudinal changes in mIDH variant allele frequencies. Enrollment continues in the phase 2 portion of this study (ENA + AZA) and the phase 3 AGILE study of IVO + AZA (NCT03173248). Clinical trial information: NCT02677922.Grade 3-4 hematological AEs. IVO 500 mg + AZA (n = 11) ENA 100 mg + AZA (n = 3) ENA 200 mg + AZA (n = 3) n Thrombocytopenia 1 0 1 Anemia 2 0 1 Febrile neutropenia 2 0 1 Neutropenia 1 0 2 Lymphocyte decrease 0 0 1 WBC decrease 0 0 1
An improved technique for calculating relative response in cellular proliferation experiments (2010)

Investigating the response of cells to specific agonists may involve the use of cell tracking dyes to assess the extent of stimulated proliferation, frequently reported as the proliferation index (PI). Calculation of PI uses a model for cell division that expects the cell number to double as cells proliferate through each successive generation. It is often useful to compare the PI of a stimulated control population with that of a population in the presence of some agent, whether chemical, pharmacologic, or cellular. For such comparison studies, the nature of the metric being used must be taken into account to accurately assess the extent of inhibition. Specifically, the metric used in ModFit LT (Verity Software House, Topsham, ME) and in FCS Express (De Novo Software, Los Angeles, CA) uses a metric with a lower limit of unity, whereas the metric used in FlowJo (Treestar, Ashland, OR) has a lower limit of zero. For studies involving cell proliferation comparisons using tracking dye dilution, a new equation is proposed as the appropriate calculation to use when determining the percent of relative response based on proliferation index values for a metric whose lower limit is unity.
Topoisomerase II-α expression increases with increasing Gleason score and with hormone insensitivity in prostate carcinoma (2006)

Topoisomerase II-alpha expression was found to increase with the known prognostic marker Gleason score and with hormone insensitivity. Objective evidence is provided for clinical trials with drugs targeting topoisomerase II-alpha to be targeted to patients with prostate cancers of Gleason Score >6 and, in particular, prostate cancers of Gleason Scores 8-10.
Engineered DNA Polymerases in Biotechnology (2010)

The latest polymerases: New DNA sequencing technologies, smart PCR strategies and reliable pathogen-detection assays most frequently rely on the performance of DNA polymerases. Directed enzyme evolution and rational design are the key steps to developing highly specialised, custom-made DNA polymerase variants. Recent achievements are reviewed.
Dynamic and quantitative Ca 2+ measurements using improved cameleons (1999)

Cameleons are genetically-encoded fluorescent indicators for Ca2+ based on green fluorescent protein variants and calmodulin (CaM). Because cameleons can be targeted genetically and imaged by one- or two-photon excitation microscopy, they offer great promise for monitoring Ca2+ in whole organisms, tissues, organelles, and submicroscopic environments in which measurements were previously impossible. However, the original cameleons suffered from significant pH interference, and their Ca2+-buffering and cross-reactivity with endogenous CaM signaling pathways was uncharacterized. We have now greatly reduced the pH-sensitivity of the cameleons by introducing mutations V68L and Q69K into the acceptor yellow green fluorescent protein. The resulting new cameleons permit Ca2+ measurements despite significant cytosolic acidification. When Ca2+ is elevated, the CaM and CaM-binding peptide fused together in a cameleon predominantly interact with each other rather than with free CaM and CaM-dependent enzymes. Therefore, if cameleons are overexpressed, the primary effect is likely to be the unavoidable increase in Ca2+ buffering rather than specific perturbation of CaM-dependent signaling.
When "Yes" Means "No": McCarran-Ferguson, the New York Convention, and the Limits of Congressional Assent (2012)

The article focuses on the awards and arbitration of the resolution of the international commercial disputes with respect to the cross-border contracts and agreements. The enactment of the McCarran-Ferguson Act of the U.S. was for the prevention of the general applicability of the federal legislation in the authority of the states for the purpose of regulating the insurance industry. Information on the decision of the Supreme Court of the U.S. regarding this issue is also presented.
Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents (2006)

This paper compares the physicochemical properties of six low molecular weight clinical complexes of gadolinium studied under identical experimental conditions. Magnevist, Dotarem, Omniscan, ProHance, MultiHance and Gadovist were investigated by oxygen-17 relaxometry at different temperatures and by proton relaxometry at various magnetic fields, temperatures and media [pure water, zinc(II)-containing aqueous solutions and HSA-containing solutions]. Osmolality, viscosity and stability versus transmetallation by zinc(II) ions were added for a more comprehensive description. The relaxivities of the clinical formulations as measured in water are similar in the imaging magnetic field region, with a slightly better performance for MultiHance. This can be explained by a shorter distance between the hydrogen nuclei of the water molecule bound to the Gd(3+) ion and this paramagnetic centre. In contrast to the open-chain complexes, all macrocyclic systems (Dotarem, ProHance and Gadovist) are insensitive to transmetallation by zinc ions. The stability of the open-chain complexes with respect to transmetallation depends on the chemical structure of the ligand, with a better stability for MultiHance. The presence of human serum albumin has no significant effect on the proton relaxivity of Magnevist, Dotarem, Omniscan, ProHance and Gadovist but markedly increases the relaxivity of MultiHance because of a non-covalent interaction with the protein. As a result, the relaxivity of MultiHance in HSA-containing media of fixed concentration decreases with increasing concentration of the contrast agent.
Human fetal neural stem cells grafted into contusion‐injured rat spinal cords improve behavior (2006)

Grafted human neural stem cells (hNSCs) may help to alleviate functional deficits resulting from spinal cord injury by bridging gaps, replacing lost neurons or oligodendrocytes, and providing neurotrophic factors. Previously, we showed that primed hNSCs differentiated into cholinergic neurons in an intact spinal cord. In this study, we tested the fate of hNSCs transplanted into a spinal cord T10 contusion injury model. When grafted into injured spinal cords of adult male rats on either the same day or 3 or 9 days after a moderate contusion injury, both primed and unprimed hNSCs survived for 3 months postengraftment only in animals that received grafts at 9 days postinjury. Histological analyses revealed that primed hNSCs tended to survive better and differentiated at higher rates into neurons and oligodendrocytes than did unprimed counterparts. Furthermore, only primed cells gave rise to cholinergic neurons. Animals receiving primed hNSC grafts on the ninth day postcontusion improved trunk stability, as determined by rearing activity measurements 3 months after grafting. This study indicates that human neural stem cell fate determination in vivo is influenced by the predifferentiation stage of stem cells prior to grafting. Furthermore, stem cell-mediated facilitation of functional improvement depends on the timing of transplantation after injury, the grafting sites, and the survival of newly differentiated neurons and oligodendrocytes.
CD146 and its Soluble Form Regulate Monocyte Transendothelial Migration (2009)

Our results demonstrate that CD146 is regulated by the inflammatory cytokine TNF and that CD146 and sCD146 are both involved in monocyte transendothelial migration during inflammation.
Protective effect of thalidomide against N‐methyl‐D‐aspartate‐induced retinal neurotoxicity (2011)

Thalidomide, an inhibitor of tumor necrosis factor-α (TNF-α) production, has been indicated to be useful for many inflammatory and oncogenic diseases. In the present study, we examined whether thalidomide (50 mg/kg/day, p.o.) has a protective effect against N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity in rats. A morphometric analysis showed that systemic administration of thalidomide protects neural cells in the ganglion cell layer (GCL) in a dose-dependent manner and significantly decreases the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in GCL and in the inner nuclear layer (INL). ELISA showed that thalidomide significantly suppressed the elevation of TNF-α 6 and 24 hr after an NMDA injection. Western blot analysis revealed a significant increase in nuclear factor-κB (NF-κB) p65 level in the retinas treated with NMDA at 24 hr after the injection, but not at 6 or 72 hr. Furthermore, an increase in p-JNK and p-p38 levels was also observed in the retina after NMDA injection. Thalidomide suppressed the increased expressions of NF-κB p65, p-JNK, and p-p38 after NMDA injection. Immunohistochemical analysis showed that thalidomide attenuated NF-κB p65 immunoreactivity in the GCL induced by NMDA treatment. In the NMDA-treated group, translocation of NF-κB p65 from the cytoplasm to the nucleus was detected in TUNEL-positive cells exposed to NMDA treatment. These results suggest new indications for thalidomide against neurodegenerative diseases.
Inhibition of Food Intake in Obese Subjects by Peptide YY3–36 (2003)

We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity.
Intrinsic sensor of oncogenic transformation induces a signal for innate immunosurveillance (2008)

Multiple cell-autonomous mechanisms exist in complex metazoans to resist oncogenic transformation, including a variety of tumor- suppressor pathways that control cell proliferation and apoptosis. In vertebrates, additional mechanisms of tumor resistance could potentially rely on cancer cell elimination by specialized cytotoxic leukocytes, such as natural killer (NK) cells. Such mechanisms would require that cancer cells be reliably distinguished from normal cells. The ligands for NKG2D, an activating NK cell receptor, are expressed on many tumor cell lines and at least some primary human tumors. However, it is unknown whether their expression is induced as a direct result of oncogenic transformation in vivo. We provide evidence that NKG2D ligands are induced on spontaneously arising tumors in a murine model of lymphomagenesis and that c-Myc is involved in their regulation. Expression of NKG2D ligands is induced at an early, distinct stage of tumorigenesis upon acquisition of genetic lesions unique to cancer cells, potentially defining a critical step in carcinogenesis. This finding suggests that the regulation of NKG2D ligands depends on a mechanism for intrinsic sensing of oncogenic transformation.
9-(Difluorophosphonoalkyl)guanines as a new class of multisubstrate analog inhibitors of purine nucleoside phosphorylase (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT9-(Difluorophosphonoalkyl)guanines as a new class of multisubstrate analog inhibitors of purine nucleoside phosphorylaseS. Halazy, A. Ehrhard, and Charles DanzinCite this: J. Am. Chem. Soc. 1991, 113, 1, 315–317Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/ja00001a045https://doi.org/10.1021/ja00001a045research-articleACS PublicationsRequest reuse permissionsArticle Views313Altmetric-Citations127LEARN 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
CSF-1 and Its Receptor in Ovarian, Endometrial and Breast Cancer (1995)

The aim of this report is to review the role of CSF-1 and its receptor in neoplasms of the breast and female reproductive tract. Expression and function of CSF-1 and its receptor were studied in tumours of the human breast, ovary and endometrium. CSF-1 and its receptor, initially implicated as essential to normal monocyte development and trophoblastic implantation, have been more recently shown to be expressed by carcinomas of the breast, ovary and endometrium where activation of the receptor by ligand produced either by the tumour cells or by stromal elements stimulates tumour cell invasion by a urokinase-dependent mechanism. Breast carcinomas express wild-type CSF-1 receptors at levels comparable to those observed in trophoblast and monocytes. Ovarian and endometrial carcinomas express significantly lower levels of wild-type, functional CSF-1Rs while ovarian carcinomas also express unusual transcripts which diverge from the wild-type CSF-1R transcript in their 5' extracellular and other sequences. Tumour cell expression of CSF-1R is under the control of several steroid hormones (glucocorticoids and progestins) and tumour cell CSF-1 expression appears to be regulated by other hormones, some of which are involved in normal lactogenic differentiation. In addition, tumour cells often produce CSF-1 at such high levels that CSF-1 spills into the extracellular fluid and circulation. Measurements of circulating levels of CSF-1 have proved useful in patients with ovarian, endometrial and breast carcinoma patients both for disease detection and monitoring of response to breast carcinoma patients both for disease detection and monitoring of response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Microarray-Based Screening for Molecular Markers in Medulloblastoma Revealed STK15 as Independent Predictor for Survival (2004)

Medulloblastoma, a primitive neuroectodermal tumor of the cerebellum, is one of the most common central nervous system malignancies of childhood. Despite aggressive multimodal therapy, including surgery, irradiation, and chemotherapy, 5-year survival rates have only approached 50-60%. To identify potential candidate genes that predict for overall survival (OS), we performed a gene expression profiling analysis in 35 newly diagnosed medulloblastoma neoplasms. Subsequently, the nine most promising candidate genes were analyzed by immunohistochemistry and fluorescence in situ hybridization on tumor tissue microarrays representing a series of 180 tumors. We found 54 genes in which expression levels predicted for unfavorable survival in medulloblastoma. In line with the gene expression profiling analysis, a positive staining for STK15 (P = 0.0006), stathmin 1 (P = 0.001), and cyclin D1 (P = 0.03) was associated with an unfavorable OS, whereas cyclin B1, DAXX, Ki-67, MYC, NRAS, and p53 showed no statistical significant effect. In comparison to clinically defined parameters such as gender, age, metastatic stage, extent of tumor resection, application of chemotherapy, and tumor grade, positive staining for STK15 was identified as an independent prognostic factor for OS (P = 0.026). Moreover, additional gene copy numbers of MYC (P = 0.003) and STK15 (P = 0.05) predicted for poor survival. The combination of gene expression profiling with tissue microarray experiments allowed the identification of a series of candidate genes that predicts for survival in medulloblastoma. Of the results highlighted by the various data analysis procedures, genes associated with cell proliferation (cyclin D1), transcription (MYC), and especially mitosis (stathmin 1, STK15) appear particularly intriguing with respect to medulloblastoma pathomechanism.
Evolution of the Integral Membrane Desaturase Gene Family in Moths and Flies (2002)

Lepidopteran insects use sex pheromones derived from fatty acids in their species-specific mate recognition system. Desaturases play a particularly prominent role in the generation of structural diversity in lepidopteran pheromone biosynthesis as a result of the diverse enzymatic properties they have evolved. These enzymes are homologous to the integral membrane desaturases, which play a primary role in cold adaptation in eukaryotic cells. In this investigation, we screened for desaturase-encoding sequences in pheromone glands of adult females of eight lepidopteran species. We found, on average, six unique desaturase-encoding sequences in moth pheromone glands, the same number as is found in the genome database of the fly, Drosophila melanogaster, vs. only one to three in other characterized eukaryotic genomes. The latter observation suggests the expansion of this gene family in insects before the divergence of lepidopteran and dipteran lineages. We present the inferred homology relationships among these sequences, analyze nonsynonymous and synonymous substitution rates for evidence of positive selection, identify sequence and structural correlates of three lineages containing characterized enzymatically distinct desaturases, and discuss the evolution of this sequence family in insects.
Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse (2010)

Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes of blindness in the developed world. RP is at present untreatable and the underlying neurodegenerative mechanisms are unknown, even though the genetic causes are often established. Acetylation and deacetylation of histones, carried out by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, affects cellular division, differentiation, death and survival. We found acetylation of histones and probably other proteins to be dramatically reduced in degenerating photoreceptors in the rd1 human homologous mouse model for RP. Using a custom developed in situ HDAC activity assay, we show that overactivation of HDAC classes I/II temporally precedes photoreceptor degeneration. Moreover, pharmacological inhibition of HDACs I/II activity in rd1 organotypic retinal explants decreased activity of poly-ADP-ribose-polymerase and strongly reduced photoreceptor cell death. These findings highlight the importance of protein acetylation for photoreceptor cell death and survival and propose certain HDAC classes as novel targets for the pharmacological intervention in RP.
A wavelength-convertible optical network (1993)

Wavelength-division multiplexing is emerging as the dominate technology in future all-optical networks. To efficiently use the wavelengths, wavelength converters are employed for a circuit-switched optical network in which a circuit can change its wavelength to resolve wavelength conflicts and to reuse the wavelengths. To improve the efficiency, a few converters are provided and shared by the incoming circuits in the share-per-node or the share-per-link wavelength-convertible switch. A heuristic algorithm for dynamic routing is used to reduce the number of converters. Performance gain in call blocking probability and fairness and in the reduction of the number of converters are shown.