gebhart/patrepeval huggingface dataset:
Apoptosis, <i>bcl</i>-2 Expression and p53 Accumulation in Myelodysplastic Syndrome, Myelodysplastic-Syndrome-Derived Acute Myelogenous Leukemia and de novo Acute Myelogenous Leukemia (1999)

Apoptosis and its dysregulation have been implicated in dysplastic and ineffective hematopoiesis and the neoplastic transformation of bone marrow in myelodysplastic syndrome (MDS). To explore the role of apoptosis in hematological disorders, we examined the frequency of apoptotic cells by the in situ end labeling method in bone marrow specimens from 37 patients with MDS [refractory anemia (RA) 10 cases, RA with excess of blasts (RAEB) 27 cases including 12 cases with leukemic transformation], 12 patients with MDS-derived acute myelogenous leukemia (AML) and 13 patients with de novo AML. In addition, we investigated the relationship of apoptosis to the immunohistochemical expression of bcl-2 and p53 in these cases, and the association of apoptosis, bcl-2, and p53 with the leukemic evolution of MDS by examining sequential bone marrow samples of the same patient from the time of initial diagnosis to the time of overt leukemia. The percentage frequency of apoptotic cells was significantly greater in MDS (RA: 9.46 +/- 2.99%, m +/- SD; RAEB: 5. 60 +/- 3.09) as compared with those in MDS-derived AML (0.62 +/- 0. 37), de novo AML (0.28 +/- 0.11) and controls (1.00 +/- 0.59). On the other hand, the cases of RAEB with leukemic transformation exhibited a lower frequency of apoptotic cells and a higher frequency of bcl-2- and p53-positive cells than those without transformation. When the RAEB cases transformed to AML, the frequency of apoptotic cells was significantly reduced (2.96 +/- 1. 54 --> 0.62 +/- 0.37), while the frequencies of bcl-2-positive cells and p53-positive cells were greater (10.88 +/- 3.66 --> 30.54 +/- 7. 14, and 20.21 +/- 6.21 --> 32.34 +/- 14.71, respectively). In contrast to MDS-derived AML, over a half of de novo AML cases showed few p53-positive cells. These findings corroborate the earlier notion that apoptosis may play a substantial role in dysplastic and ineffective hematopoiesis in MDS. It is also suggested that the suppression of apoptosis associated with enhanced bcl-2 expression and p53 accumulation increases the probability of developing leukemia in MDS, and that oncogenetic development might be different between MDS-derived AML and de novo AML.
马克思关于“自然是人的无机的身体”之命题 (1998)

按照马克思的说法,“自然是人的无机的身体”。我们该如何来理解这一图景呢?根据近来某些观察家们的观点,马克思的上述论断所表述的自然概念是生态自然概念,按照其中的一位评论家的说法,马克思的这一观念蕴含着,“就人这一有意识的社会存在而言,他理所当然地会为了所有物种的利益而合理地、有意识地行事,这样做也是为了人自身的长远利益,因为自然是人的机体”。然而,正是把自然视为“人的无机的身体”的同一个马克思,同样把“机车、铁路、电报、自动走锭精纺机等等”描述为“人类头脑的器官”。充其量来说,我们在此似乎遇到了一种受到极大曲解的身体意识。 然而,我们也许不应如此鲁莽地将马克思的思想进行肢解。正如华滋华斯警告我们提防鲁莽的分析精神,他说“这是谋杀和肢解”。与此相反,我们应当完整地把握马克思关于自然的概念,及其同马克思更大的问题的关系。如果这样,我们就会发现存在比这些相互冲突的身体形象所表明的更多的一致性,并发现存在比许多人也许会提出疑义的还更为深刻的矛盾。
A novel approach to fast multi-block motion estimation for H.264 video coding (2003)

The upcoming video coding standard, H.264, uses motion estimation with multiple block sizes to improve the rate-distortion performance. However, full exhaustive search of all block sizes is computational intensive with complexity increasing linearly with the number of allowed block size. In this paper, a novel fast multi-block motion estimation (FMBME) is proposed for H.264 video coding. Experimental results show that the proposed FMBME can efficiently reduce the computational cost by 40.73% with similar visual quality and bit rate.
Photochemically and photoenzymatically cleavable DNA (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotochemically and photoenzymatically cleavable DNASourena Nadji, Cheng I. Wang, and John Stephen TaylorCite this: J. Am. Chem. Soc. 1992, 114, 24, 9266–9269Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/ja00050a003https://doi.org/10.1021/ja00050a003research-articleACS PublicationsRequest reuse permissionsArticle Views209Altmetric-Citations17LEARN 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
Copper transport into the secretory pathway is regulated by oxygen in macrophages (2009)

Copper is an essential nutrient for a variety of biochemical processes; however, the redox properties of copper also make it potentially toxic in the free form. Consequently, the uptake and intracellular distribution of this metal is strictly regulated. This raises the issue of whether specific pathophysiological conditions can promote adaptive changes in intracellular copper distribution. In this study, we demonstrate that oxygen limitation promotes a series of striking alterations in copper homeostasis in RAW264.7 macrophage cells. Hypoxia was found to stimulate copper uptake and to increase the expression of the copper importer, CTR1. This resulted in increased copper delivery to the ATP7A copper transporter and copper-dependent trafficking of ATP7A to cytoplasmic vesicles. Significantly, the ATP7A protein was required to deliver copper into the secretory pathway to ceruloplasmin, a secreted copperdependent enzyme, the expression and activity of which were stimulated by hypoxia. However, the activities of the alternative targets of intracellular copper delivery, superoxide dismutase and cytochrome c oxidase, were markedly reduced in response to hypoxia. Collectively, these findings demonstrate that copper delivery into the biosynthetic secretory pathway is regulated by oxygen availability in macrophages by a selective increase in copper transport involving ATP7A.
FcγRs Modulate Cytotoxicity of Anti-Fas Antibodies: Implications for Agonistic Antibody-Based Therapeutics (2003)

Development of anti-Fas Abs to treat diseases with insufficient Fas-mediated apoptosis has been limited by concern about hepatotoxicity. We report here that hepatotoxicity elicited by anti-Fas Ab Jo2 is dependent on FcgammaRIIB. Thus, following Jo2 treatment, all FcgammaRIIB(-/-) mice survived while 80% of wild-type and all FcR-gamma(-/-) mice died from acute liver failure. Microscopic examination suggests that FcgammaRIIB deficiency protects the hepatic sinusoidal endothelium, a cell type that normally coexpresses Fas and FcgammaRIIB. In vitro studies showed that FcgammaRIIB, but not FcgammaRI and FcgammaRIII, on neighboring macrophages substantially enhanced Jo2 mediated apoptosis of Fas expressing target cells. However, FcgammaRI and FcgammaRIII appeared essential for apoptosis-inducing activity of a non-hepatotoxic anti-Fas mAb HFE7A. These findings imply that by interacting with the Fc region of agonistic Abs, FcgammaRs can modulate both the desired and undesired consequences of Ab-based therapy. Recognizing this fact should facilitate development of safer and more efficacious agonistic Abs.
Rotating polarization imaging in turbid media (1996)

It is shown experimentally that one can image an object embedded in a turbid medium by probing the medium with light with a rotating linear polarization. This method permits the ballistic photons to be isolated from the large background of photons that have been multiply scattered by optically dense anisotropic scatterers. This technique achieves a good signal-to-noise ratio even with a low-power continuous laser, leading to images with a diffraction-limited resolution comparable with that obtained in optically homogeneous media.
Structure and Catalytic Properties of Carboxylesterase Isozymes Involved in Metabolic Activation of Prodrugs (2008)

Mammalian carboxylesterases (CESs) comprise a multigene family whose gene products play important roles in biotransformation of ester- or amide-type prodrugs. They are members of an alpha,beta-hydrolase-fold family and are found in various mammals. It has been suggested that CESs can be classified into five major groups denominated CES1-CES5, according to the homology of the amino acid sequence, and the majority of CESs that have been identified belong to the CES1 or CES2 family. The substrate specificities of CES1 and CES2 are significantly different. The CES1 isozyme mainly hydrolyzes a substrate with as mall alcohol group and large acyl group, but its wide active pocket sometimes allows it to act on structurally distinct compounds of either a large or small alcohol moiety. In contrast, the CES2 isozyme recognizes a substrate with a large alcohol group and small acyl group, and its substrate specificity may be restricted by the capability of acyl-enzyme conjugate formation due to the presence of conformational interference in the active pocket. Since pharmacokinetic and pharmacological data for prodrugs obtained from preclinical experiments using various animals are generally used as references for human studies, it is important to clarify the biochemical properties of CES isozymes. Further experimentation for an understanding of detailed substrate specificity of prodrugs for CES isozymes and its hydrolysates will help us to design the ideal prodrugs.
Intelligent scissors for image composition (1995)

We present a new, interactive tool called Intelligent Scissors which we use for image segmentation and composition. Fully automated segmentation is an unsolved problem, while manual tracing is inaccurate and laboriously unacceptable. However, Intelligent Scissors allow objects within digital images to be extracted quickly and accurately using simple gesture motions with a mouse. When the gestured mouse position comes in proximity to an object edge, a live-wire boundary "snaps" to, and wraps around the object of interest.
A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity. (1992)

Several domains of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein have been identified that are involved in HIV-1-mediated membrane fusion. One domain that is involved in membrane fusion is the hydrophobic amino terminus of the HIV-1 transmembrane glycoprotein gp41. Here we show that a polar substitution at gp41 amino acid 2 (the 41.2 mutation) results in an envelope glycoprotein that dominantly interferes with both syncytium formation and infection mediated by the wild-type HIV-1 envelope glycoprotein. The interference by the 41.2 mutant is not a result of aberrant envelope glycoprotein synthesis, processing, or transport. The 41.2 mutant elicits a dominant interfering effect even in the presence of excess wild-type glycoprotein, suggesting that a higher-order envelope glycoprotein complex is involved in membrane fusion. These results shed light on the process by which the HIV-1 envelope glycoproteins induce membrane fusion reactions and present a possible approach to anti-HIV therapy.
Short Communication : Studies in Macaques on Cross-Clade T Cell Responses Elicited by a DNA/MVA AIDS Vaccine, Better Conservation of CD8 Than CD4 T Cell Responses (2005)

One of the unknowns faced by an HIV/AIDS vaccine is the ability of a single clade vaccine to protect against the multiple genetic subtypes and recombinant forms of HIV-1 present in the current pandemic. Here, we use a macaque model to investigate the ability of our clade B vaccine that consists of DNA priming and modified vaccinia Ankara (MVA) virus boosting to elicit T cell responses that recognize an A/G recombinant of HIV-1. To test for cross-reactive T cells, intracellular cytokine staining was conducted using five pools of Gag and six pools of Env peptides representing B or A/G sequences. Studies using the peptide pools revealed essentially complete conservation of the CD8 response but only approximately 50% conservation of the CD4 response. Thus, the ability of an HIV vaccine for one clade to protect against other clades may be more limited by the ability to provide CD4 T cell help than the ability to elicit CD8 effector functions.
Expression of cholera toxin B–proinsulin fusion protein in lettuce and tobacco chloroplasts – oral administration protects against development of insulitis in non‐obese diabetic mice (2007)

Lettuce and tobacco chloroplast transgenic lines expressing the cholera toxin B subunit-human proinsulin (CTB-Pins) fusion protein were generated. CTB-Pins accumulated up to ~16% of total soluble protein (TSP) in tobacco and up to ~2.5% of TSP in lettuce. Eight milligrams of powdered tobacco leaf material expressing CTB-Pins or, as negative controls, CTB-green fluorescent protein (CTB-GFP) or interferon-GFP (IFN-GFP), or untransformed leaf, were administered orally, each week for 7 weeks, to 5-week-old female non-obese diabetic (NOD) mice. The pancreas of CTB-Pins-treated mice showed decreased infiltration of cells characteristic of lymphocytes (insulitis); insulin-producing beta-cells in the pancreatic islets of CTB-Pins-treated mice were significantly preserved, with lower blood or urine glucose levels, by contrast with the few beta-cells remaining in the pancreatic islets of the negative controls. Increased expression of immunosuppressive cytokines, such as interleukin-4 and interleukin-10 (IL-4 and IL-10), was observed in the pancreas of CTB-Pins-treated NOD mice. Serum levels of immunoglobulin G1 (IgG1), but not IgG2a, were elevated in CTB-Pins-treated mice. Taken together, T-helper 2 (Th2) lymphocyte-mediated oral tolerance is a likely mechanism for the prevention of pancreatic insulitis and the preservation of insulin-producing beta-cells. This is the first report of expression of a therapeutic protein in transgenic chloroplasts of an edible crop. Transplastomic lettuce plants expressing CTB-Pins grew normally and transgenes were maternally inherited in T(1) progeny. This opens up the possibility for the low-cost production and delivery of human therapeutic proteins, and a strategy for the treatment of various other autoimmune diseases.
Identification and Characterization of Small-Molecule Inhibitors of the R132H/R132H Mutant Isocitrate Dehydrogenase 1 Homodimer and R132H/Wild-Type Heterodimer (2014)

Recurrent genetic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been identified in multiple tumor types. The most frequent mutation, IDH1 R132H, is a gain-of-function mutation resulting in an enzyme-catalyzing conversion of α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG). A high-throughput assay quantifying consumption of NADPH by IDH1 R132H has been optimized and implemented to screen 3 million compounds in 1536-well formats. The primary high-throughput screening hits were further characterized by RapidFire-mass spectrometry measuring 2-HG directly. Multiple distinct chemotypes were identified with nanomolar potencies (6-300 nM). All inhibitors were found to be inactive against the wild-type IDH1 homodimers. An IDH1 heterodimer between wild-type and R132H mutant is capable of catalyzing conversion of α-KG to 2-HG and isocitrate to α-KG. Interestingly, one of the inhibitors, EXEL-9324, was found to inhibit both conversions by the IDH1 heterodimer. This indicates the R132H/WT heterodimer may adopt conformations distinct from that of the R132H/R132H homodimer. Further enzymatic studies support this conclusion as the heterodimer exhibited a significantly lower apparent Michaelis-Menten constant for α-KG (K(m)=110 µM) compared with the R132H homodimer (K(m)= 1200 µM). The enhanced apparent affinity for α-KG suggests R132H/WT heterodimeric IDH1 can produce 2-HG more efficiently at normal intracellular levels of α-KG (approximately 100 µM).
Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in Choline Deficient Diet Fed Rats (2003)

1) Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet; 2)Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.
Label-free DNA imaging in vivo with stimulated Raman scattering microscopy (2015)

Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based on changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Furthermore, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. Our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time.
Generative Models of Visually Grounded Imagination (2017)

It is easy for people to imagine what a man with pink hair looks like, even if they have never seen such a person before. We call the ability to create images of novel semantic concepts visually grounded imagination. In this paper, we show how we can modify variational auto-encoders to perform this task. Our method uses a novel training objective, and a novel product-of-experts inference network, which can handle partially specified (abstract) concepts in a principled and efficient way. We also propose a set of easy-to-compute evaluation metrics that capture our intuitive notions of what it means to have good visual imagination, namely correctness, coverage, and compositionality (the 3 C's). Finally, we perform a detailed comparison of our method with two existing joint image-attribute VAE methods (the JMVAE method of Suzuki et.al. and the BiVCCA method of Wang et.al.) by applying them to two datasets: the MNIST-with-attributes dataset (which we introduce here), and the CelebA dataset.
Synthesis of Some Novel 4‐Substituted Coumarins Having Potential Biological Activity. Part 2. (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Electromyographic Findings in Focal Laryngeal Dystonia (Spastic Dysphonia) (1985)

Spastic dysphonia is a clinical speech disorder characterized by spasms of the laryngeal muscles during phonation, producing a broken pattern of speech sometimes termed laryngeal stuttering. Fourteen patients with the diagnosis of spastic dysphonia based on voice quality were referred for evaluation; detailed clinical and electrophysiologic evaluations were performed. Laryngeal electromyographic (EMG) testing failed to demonstrate any spontaneous activity in the 14 patients tested. Seven patients (50%) had normal number and amplitude of motor unit potentials. Four of these had disparate amplitudes when compared with the other side, and two had complex motor unit potentials. The other seven patients (50%) had abnormal findings, including three patients with abnormally increased amplitude. Two patients had asynchronous activity characteristic of a tremor disorder. One patient had synchronous bursts of activity also affecting the diaphragm, later diagnosed as pyramidal and extrapyramidal disease. One patient had bursts of activity, and later presented with diffuse myoclonus. Laryngeal EMG therefore seemed to be a more precise way of evaluating patients presenting with a tremulous voice pattern termed spastic dysphonia. Clinical observation and EMG data demonstrated that spastic dysphonia is not a "spastic" disease. We identified patients with tremor (2), pyramidal and extrapyramidal disease (1), and myoclonic disorders (1). The remainder of the patients had clinical and EMG findings consistent with dystonia, a neurologic disorder characterized by abnormal, often action-induced, involuntary movements or uncontrolled spasms. We classify these patients as having "focal laryngeal dystonia" when the disorder occurs in isolation. It may also present as a component of a generalized dystonic syndrome.
Convenient synthesis of l.alpha.-hydroxy-vitamin D3 (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConvenient synthesis of l.alpha.-hydroxy-vitamin D3D. H. R. Barton, R. H. Hesse, M. M. Pechet, and E. RizzardoCite this: J. Am. Chem. Soc. 1973, 95, 8, 2748–2749Publication Date (Print):April 1, 1973Publication History Published online1 May 2002Published inissue 1 April 1973https://pubs.acs.org/doi/10.1021/ja00789a090https://doi.org/10.1021/ja00789a090research-articleACS PublicationsRequest reuse permissionsArticle Views557Altmetric-Citations122LEARN 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
Optical imaging by means of two-photon quantum entanglement (1995)

A two-photon optical imaging experiment was performed based on the quantum nature of the signal and idler photon pairs produced in spontaneous parametric down-conversion. An aperture placed in front of a fixed detector is illuminated by the signal beam through a convex lens. A sharp magnified image of the aperture is found in the coincidence counting rate when a mobile detector is scanned in the transverse plane of the idler beam at a specific distance in relation to the lens.