gebhart/patrepeval huggingface dataset:
beta-VAE: Learning Basic Visual Concepts with a Constrained Variational Framework (2017)

Learning an interpretable factorised representation of the independent data generative factors of the world without supervision is an important precursor for the development of artificial intelligence that is able to learn and reason in the same way that humans do. We introduce beta-VAE, a new state-of-the-art framework for automated discovery of interpretable factorised latent representations from raw image data in a completely unsupervised manner. Our approach is a modification of the variational autoencoder (VAE) framework. We introduce an adjustable hyperparameter beta that balances latent channel capacity and independence constraints with reconstruction accuracy. We demonstrate that beta-VAE with appropriately tuned beta > 1 qualitatively outperforms VAE (beta = 1), as well as state of the art unsupervised (InfoGAN) and semi-supervised (DC-IGN) approaches to disentangled factor learning on a variety of datasets (celebA, faces and chairs). Furthermore, we devise a protocol to quantitatively compare the degree of disentanglement learnt by different models, and show that our approach also significantly outperforms all baselines quantitatively. Unlike InfoGAN, beta-VAE is stable to train, makes few assumptions about the data and relies on tuning a single hyperparameter, which can be directly optimised through a hyper parameter search using weakly labelled data or through heuristic visual inspection for purely unsupervised data.
Conformational studies of nucleoprotein. Circular dichroism of deoxyribonucleic acid base pairs bound by polylysine (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformational studies of nucleoprotein. Circular dichroism of deoxyribonucleic acid base pairs bound by polylysineCatherine Chang, Manuel Weiskopf, and Hsueh Jei LiCite this: Biochemistry 1973, 12, 16, 3028–3032Publication Date (Print):July 1, 1973Publication History Published online1 May 2002Published inissue 1 July 1973https://pubs.acs.org/doi/10.1021/bi00740a013https://doi.org/10.1021/bi00740a013research-articleACS PublicationsRequest reuse permissionsArticle Views78Altmetric-Citations36LEARN 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
Very Long-chain Acyl-CoA Synthetases (2000)

Activation by thioesterification to coenzyme A is a prerequisite for most reactions involving fatty acids. Enzymes catalyzing activation, acyl-CoA synthetases, have been classified by their chain length specificities. The most recently identified family is the very long-chain acyl-CoA synthetases (VLCS). Although several members of this group are capable of activating very long-chain fatty acids (VLCFA), one is a bile acid-CoA synthetase, and others have been characterized as fatty acid transport proteins. It was reported that the Drosophila melanogaster mutant bubblegum (BGM) had elevated VLCFA and that the product of the defective gene had sequence homology to acyl-CoA synthetases. Therefore, we cloned full-length cDNA for a human homolog of BGM, and we investigated the properties of its protein product, hsBG, to determine whether it had VLCS activity. Northern blot analysis showed that hsBG is expressed primarily in brain. Compared with vector-transfected cells, COS-1 cells expressing hsBG had increased acyl-CoA synthetase activity with either long-chain fatty acid (2.4-fold) or VLCFA (2.6-fold) substrates. Despite this increased VLCFA activation, hsBG-expressing cells did not have increased rates of VLCFA degradation. Confocal microscopy showed that hsBG had a cytoplasmic localization in some COS-1 cells expressing the protein, whereas it appeared to associate with plasma membrane in others. Fractionation of these cells revealed that most of the hsBG-dependent acyl-CoA synthetase activity was soluble and not membrane-bound. Immunoaffinity-purified hsBG from transfected COS-1 cells was enzymatically active. hsBG and hsVLCS are only 15% identical, and comparison with sequences of two conserved motifs from all known families of acyl-CoA synthetases revealed that hsBG along with the D. melanogaster and murine homologs comprise a new family of acyl-CoA synthetases. Thus, two protein families are now known that contain enzymes capable of activating VLCFA. Because hsBG is expressed in brain but previously described VLCSs were not highly expressed in this organ, hsBG may play a central role in brain VLCFA metabolism and myelinogenesis.
Synthesis and Bio-activity of 1-(9H-Carbazol-4-yloxy)-3-Substituted Amino-2-Propanol Compounds II. (2001)

AIM The purpose is to make a search for new compounds with β-adrenergic recepotor antagonistic action. METHOD Using carazolol as a lead compound, the 1-(9H-carbazol-4-yloxy)-3-substituted amino-2-propanol compounds were designed and synthesized, all of which were not reported previously. Their structures were identified by IR, 1HNMR, EA or HRMS. RESULTS AND CONCLUSION The preliminary biological tests suggested that all the ten compounds could inhibit isoprenaline-induced tachycardia to different extent, and three of them showed better activity.
Lab-on-a-Chip Immunoassay for Multiple Antibodies Using Microsphere Light Scattering and Quantum Dot Emission (2007)

Detection of multiple biomarkers has recently received great interest from the biosensors community. These diagnostic methods must be rapid, specific, sensitive, and cost-effective. In 2006, our group demonstrated a successful lab-on-a-chip immunoassay using microsphere light scattering, which is essentially a one-step, automated protocol, on a reusable chip. In the past, this had been difficult due to the limitations of microfluidic mixing and false-positive readings of particle immunoassays in a chip environment. In this current study, we conjugated quantum dots (QDs) onto microspheres to enable multiplex assays as well as to enhance the limit of detection (LOD). We named this configuration nano-on-micro or NOM. Upon radiation with UV light (380 nm), a stronger light scattering signal is observed with NOMs than QDs or microspheres alone. Additionally, NOMs are easier to handle than QDs. Since QDs also provide fluorescent emission, we are able to utilize an increase in light scattering for detecting antigen-antibody reaction and a decrease in QD emission to identify which antibody (or antigen) is present. Two types of NOM combinations were used. One batch of microspheres was coated with QDs emitting at 655 nm and mouse IgG (mIgG); the other with QDs emitting at 605 nm and bovine serum albumin (BSA). A mixture of these two NOMs was used to identify either anti-mIgG or anti-BSA. NOM particles and target solutions were mixed in a microfluidic device and on-chip detection was performed using proximity optical fibers. Forward light scattering at 380 nm was collected. With the positive target, the scattering signal was increased. The LOD was 25 ng ml-1 (165 pM) with p<0.05. Fluorescent emission (655 or 605 nm) was simultaneously collected. With the positive target, the emission signal was attenuated. Therefore, we were able to detect two different antibodies simultaneously with two different detection protocols. We believe this NOM bioassay has the ability to screen for and detect multiple antibodies with minimal sample processing and handling.
B‐type Eph receptors and ephrins induce growth cone collapse through distinct intracellular pathways (2003)

Forward and reverse signaling mediated by EphB tyrosine kinase receptors and their transmembrane ephrin-B ligands play important roles in axon pathfinding, yet little is known about the intracellular pathways involved. Here we have used growth cones from the ventral (EphB receptor-bearing) and dorsal (ephrin-B-bearing) embryonic Xenopus retina to investigate the signaling mechanisms in both forward and reverse directions. We report that unclustered, but not clustered, EphB2 ectodomains trigger fast (5-10 min) transient collapse responses in growth cones. This collapse response is mediated by low levels of intracellular cyclic GMP and requires proteasome function. In contrast, clustered, but not unclustered, ephrin-B1 ectodomains cause slow (30-60 min) growth cone collapse that depends on high cGMP levels and is insensitive to inhibition of the proteasomal pathway. Upon receptor-ligand binding, endocytosis occurs in the reverse direction (EphB2-Fc into dorsal retinal growth cones), but not the forward direction, and is also sensitive to proteasomal inhibition. Endocytosis is functionally important because blocking of EphB2 internalization inhibits growth cone collapse. Our data reveal that distinct signaling mechanisms exist for B-type Eph/ephrin-mediated growth cone guidance and suggest that endocytosis provides a fast mechanism for switching off signaling in the reverse direction.
Selenite Induces Posttranscriptional Blockade of HLA-E Expression and Sensitizes Tumor Cells to CD94/NKG2A-Positive NK Cells (2011)

CD94/NKG2A is an inhibitory receptor that controls the activity of a large proportion of human NK cells following interactions with the nonclassical HLA class Ib molecule HLA-E expressed on target cells. In this study, we show that selenite (SeO(3)(2-)), an inorganic selenium compound, induces an almost complete loss of cell surface expression of HLA-E on tumor cells of various origins. Selenite abrogated the HLA-E expression at a posttranscriptional level, since selenite exposure led to a dose-dependent decrease in cellular HLA-E protein expression whereas the mRNA levels remained intact. The loss of HLA-E expression following selenite treatment was associated with decreased levels of intracellular free thiols in the tumor cells, suggesting that the reduced HLA-E protein synthesis was caused by oxidative stress. Indeed, HLA-E expression and the level of free thiols remained intact following treatment with selenomethionine, a selenium compound that does not generate oxidative stress. Loss of HLA-E expression, but not of total HLA class I expression, on tumor cells resulted in increased susceptibility to CD94/NK group 2A-positive NK cells. Our results suggest that selenite may be used to potentiate the anti-tumor cytotoxicity in settings of NK cell-based immunotherapies.
Identification of a 21 amino acid peptide conferring 3‐hydroxypropionic acid stress‐tolerance to Escherichia coli (2011)

We report the identification of a novel small open reading frame in Escherichia coli. The sORF (called iroK) encodes a 21 amino cid peptide, which when translated confers a 133% (ca. 20 g/L) increase in resistance to 3-hydroxypropionic acid. We show that iroK conferred tolerance is additive to previously identified tolerance mechanisms involving relief of inhibited metabolism, yet does not involve altered 3-HP transport. This result demonstrates the continued surprises that microbial genomes hold and emphasize the importance of comprehensive discovery methods in future strain and metabolic engineering efforts.
G364R mutation of MCM4 detected in human skin cancer cells affects DNA helicase activity of MCM4/6/7 complex (2015)

A number of gene mutations are detected in cells derived from human cancer tissues, but roles of these mutations in cancer cell development are largely unknown. We examined G364R mutation of MCM4 detected in human skin cancer cells. Formation of MCM4/6/7 complex is not affected by the mutation. Consistent with this notion, the binding to MCM6 is comparable between the mutant MCM4 and wild-type MCM4. Nuclear localization of this mutant MCM4 expressed in HeLa cells supports this conclusion. Purified MCM4/6/7 complex containing the G364R MCM4 exhibited similar levels of single-stranded DNA binding and ATPase activities to the complex containing wild-type MCM4. However, the mutant complex showed only 30-50% of DNA helicase activity of the wild-type complex. When G364R MCM4 was expressed in HeLa cells, it was fractionated into nuclease-sensitive chromatin fraction, similar to wild-type MCM4. These results suggest that this mutation does not affect assembly of MCM2-7 complex on replication origins but it interferes some step at function of MCM2-7 helicase. Thus, this mutation may contribute to cancer cell development by disturbing DNA replication.
Georges Perec's experiments in social description (2001)

This article dissects some key works, published in the 1960s and 1970s, by French writer Georges Perec to argue that they can be understood, in different ways, as forms of ethnographic writing utilizing approaches, methods and stylistic devices which remain highly pertinent to ethnographic practices today. The devices in Perec's repertoire include minutely detailed descriptions, lists, the use of imperfect and conditional tenses, significant but mundane exemplars. In acute form, Perec demonstrates the necessary tensions between the presentation of detail, the role of generalization and the need for explanation in our `tellings about society'.
Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson's disease (2002)

We assessed the safety and efficacy of modafinil for the treatment of excessive daytime sleepiness in patients with Parkinson's disease (PD). This was a single-site, randomized, double-blind, placebo-controlled crossover study of 21 PD patients having an Epworth Sleepiness Scale (ESS) score > or =10. They received either placebo or modafinil 200 mg/day for 3 weeks, followed by a washout week, then the alternate treatment for 3 weeks. The ESS data demonstrated a carryover effect, so the changes from baseline ESS scores were compared between the two treatments for period 1 only. The ESS scores for the placebo group went from 16.0 +/- 4.2 (mean +/- SD) to 17.0 +/- 5.1 and for the modafinil group went from 17.8 +/- 4.2 to 14.4 +/- 5.7 (P = 0.039). There was no significant carryover effect for any other measure. The patient Clinical Global Impression of Change (+3 to -3) improved by 0.75 on modafinil compared with 0.15 for placebo (P = 0.07). A total of 7 of 20 (35%) of the patients reported some improvement on modafinil but not placebo. There was no significant improvement or worsening of the UPDRS subscores I-III, Timed Tap test, or time on. Vital signs, electrocardiograms, and lab tests were unchanged. Modafinil was very well tolerated. Our data demonstrate that, in a small sample size, administration of 200 mg/day of modafinil was associated with few side effects and was modestly effective for the treatment of excessive daytime sleepiness in patients with PD.
Genetically engineered rice resistant to rice stripe virus, an insect-transmitted virus. (1992)

The coat protein (CP) gene of rice stripe virus was introduced into two japonica varieties of rice by electroporation of protoplasts. The resultant transgenic plants expressed the CP at high levels (up to 0.5% of total soluble protein) and exhibited a significant level of resistance to virus infection. Plants derived from selfed progeny of the primary transformants also expressed the CP and showed viral resistance, indicating stable transmission of the CP gene and the trait of resistance to the next generation. Moreover, the virally encoded strip disease-specific protein was not detected in transgenic plants expressing CP 8 weeks after inoculation, indicating protection before viral multiplication. These studies demonstrated that CP-mediated resistance to virus infection can be extended to cereals and to the viruses transmitted by an insect vector (planthopper).
The molecular structure of UDP‐galactose 4‐epimerase from Escherichia coli determined at 2.5 Å resolution (1992)

UDP-galactose 4-epimerase catalyzes the conversion of UDP-galactose to UDP-glucose during normal galactose metabolism. The molecular structure of UDP-galactose 4-epimerase from Escherichia coli has now been solved to a nominal resolution of 2.5 A. As isolated from E. coli, the molecule is a dimer of chemically identical subunits with a total molecular weight of 79,000. Crystals of the enzyme used for this investigation were grown as a complex with the substrate analogue, UDP-benzene, and belonged to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 76.3 A, b = 83.1 A, c = 132.1 A, and one dimer per asymmetric unit. An interpretable electron density map calculated to 2.5 A resolution was obtained by a combination of multiple isomorphous replacement with six heavy atom derivatives, molecular averaging, and solvent flattening. Each subunit of epimerase is divided into two domains. The larger N-terminal domain, composed of amino acid residues 1-180, shows a classic NAD+ binding motif with seven strands of parallel beta-pleated sheet flanked on either side of alpha-helices. The seventh strand of the beta-pleated sheet is contributed by amino acid residues from the smaller domain. In addition, this smaller C-terminal domain, consisting of amino acid residues 181-338, contains three strands of beta-pleated sheet, two major alpha-helices and one helical turn. The substrate analogue, UDP-benzene, binds in the cleft located between the two domains with its phenyl ring in close proximity to the nicotinamide ring of NAD+. Contrary to the extensive biochemical literature suggesting that epimerase binds only one NAD+ per functional dimer, the map clearly shows electron density for two nicotinamide cofactors binding in symmetry-related positions in the dimer. Likewise, each subunit in the dimer also binds one substrate analogue.
ZD1839 (IressaTM): For More Than Just Non-Small Cell Lung Cancer (2002)

) is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal transduction pathways involved in cell proliferation. Preclinical studies demonstrated that ZD1839 is a promising agent for the treatment of a wide range of tumors and has additive-to-synergistic effects when combined with radiation or chemotherapy in various cell lines and xenografts. Phase I clinical trials have reported that ZD1839 has acceptable tolerability and antitumor activity. In addition to non-small cell lung cancer, phase II/III studies are currently investigating ZD1839 as monotherapy or in combination therapy against prostate, breast, head and neck, gastric, and colorectal tumors.
Cloning and mapping of BamHi endonuclease fragments of DNA from the transforming B95-8 strain of Epstein-Barr virus. (1980)

DNA from the B95-8 strain of Epstein-Barr virus was cleaved into 29 different fragments by BamHI endonuclease (EC 3.1.23.6). All of the fragments except the terminal fragments have been inserted into the pBR322 cloning vector and replicated in Escherichia coli. The location of each cloned DNA fragment in the viral genome has been determined, providing a more detailed physical map of the genome than has been available previously.
Perispinal etanercept: a new therapeutic paradigm in neurology (2010)

Etanercept is a potent antagonist of TNF, a pleotropic immune signaling molecule that is also a pivotal regulator of synaptic function. Excess TNF is centrally involved in the pathogenesis of a variety of inflammatory neurological disorders, including Alzheimer's disease, sciatica, traumatic brain injury and spinal cord injury. Perispinal etanercept produces rapid improvement in both Alzheimer's disease and sciatica and in other forms of disc-related pain. Basic research and the observed clinical effects suggest that etanercept has the surprising ability to penetrate into the cerebrospinal fluid after perispinal administration. Perispinal administration is a novel method of delivery designed to introduce this anti-TNF molecule into the bidirectional cerebrospinal venous system and the cerebrospinal fluid to facilitate its selective delivery to either spinal structures or the brain. The scientific rationale, physiologic mechanisms, clinical effects and potential clinical indications of this therapeutic approach are the subject of this article.
Preparation of type III procollagen and collagen from rat skin (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticlePreparation of type III procollagen and collagen from rat skinPeter H. Byers, Keith H. McKenney, Jack R. Lichtenstein, and George R. MartinCite this: Biochemistry 1974, 13, 25, 5243–5248Publication Date (Print):December 1, 1974Publication History Published online1 May 2002Published inissue 1 December 1974https://pubs.acs.org/doi/10.1021/bi00722a030https://doi.org/10.1021/bi00722a030research-articleACS PublicationsRequest reuse permissionsArticle Views194Altmetric-Citations120LEARN 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