gebhart/patrepeval huggingface dataset:
A mammalian two-hybrid system for adenomatous polyposis coli-mutated colon cancer therapeutics. (2001)

Colon cancer cells frequently lose expression of the tumor suppressor adenomatous polyposis coli (APC). As result, beta-catenin accumulates and activates transcription of Tcf-responsive genes. Here we describe a novel mammalian two-hybrid system that selectively kills APC-mutated cells. This system consists of GAL4/beta-catenin, VP16/Tcf4, and a gene that is transcribed when GAL4 and VP16 associate. In APC-mutated human colon cancer cells, such as SW480, GAL4/beta-catenin accumulates, and in the presence of VP16/Tcf4, induces high levels of expression of the reporter gene. Expression of wild-type APC reduced GAL4/beta-catenin and intact beta-catenin levels and inhibited reporter gene expression. In colon cancer cells such as SW48 that have wild-type APC, GAL4/beta-catenin was degraded, and expression levels of the output gene were low. Replacement of the reporter gene with a suicide gene resulted in selective killing of SW480 cells. This system may be applicable for broader use of gene therapy by targeting diseases that involve protein degradation.
Increasing the potency of a cytotoxin with an arginine graft (2007)

Variants and homologs of bovine pancreatic ribonuclease (RNase A) can exhibit cytotoxic activity. This toxicity relies on cellular internalization of the enzyme. Residues Glu49 and Asp53 form an anionic patch on the surface of RNase A. We find that replacing these two residues with arginine does not affect catalytic activity or affinity for the cytosolic ribonuclease inhibitor (RI) protein. This 'arginine graft' does, however, increase toxicity towards human cancer cells. Appending a nonaarginine domain to this cationic variant results in an additional increase in cytotoxicity, providing one of the most cytotoxic known variants of RNase A. These findings correlate the potency of a ribonuclease with its deliverance of ribonucleolytic activity to the cytosol, and indicate a rational means to enhance the efficacy of ribonucleases and other cytotoxic proteins.
Peptides : synthesis, structures, and applications (1995)

(Chapter Headings) the History of Peptide Chemistry. Amide Formation, Deprotection, And Disulfide Formation in Peptide Synthesis. Solid Phase Peptide Synthesis. A-Helix Formation By Peptides in Water. Peptide Conformation: Stability and Dynamics. Structure-Function Studies of Peptide Hormones: An Overview. Neuropeptides: Peptides and Nonpeptide Analogs. Reversible Inhibitors of Serine Proteinases, Naturallly Occurring Miniproteins, Semisynthetic Variants, Recombinant Homologues and Synthetic Peptides. Design of Polypeptides. Chemical Combinatorial Libraries: Current Capabilities and Future Possibilities. Epitope Mapping with Peptides. Active Immunization Using Synthetic Peptides.
Evolutionary Neural AutoML for Deep Learning (2019)

Deep neural networks (DNNs) have produced state-of-the-art results in many benchmarks and problem domains. However, the success of DNNs depends on the proper configuration of its architecture and hyperparameters. Such a configuration is difficult and as a result, DNNs are often not used to their full potential. In addition, DNNs in commercial applications often need to satisfy real-world design constraints such as size or number of parameters. To make configuration easier, automatic machine learning (AutoML) systems for deep learning have been developed, focusing mostly on optimization of hyperparameters. This paper takes AutoML a step further. It introduces an evolutionary AutoML framework called LEAF that not only optimizes hyperparameters but also network architectures and the size of the network. LEAF makes use of both state-of-the-art evolutionary algorithms (EAs) and distributed computing frameworks. Experimental results on medical image classification and natural language analysis show that the framework can be used to achieve state-of-the-art performance. In particular, LEAF demonstrates that architecture optimization provides a significant boost over hyperparameter optimization, and that networks can be minimized at the same time with little drop in performance. LEAF therefore forms a foundation for democratizing and improving AI, as well as making AI practical in future applications.
Clinical Overview of Algal-Docosahexaenoic Acid: Effects on Triglyceride Levels and Other Cardiovascular Risk Factors (2009)

The cardiovascular benefits of fish-derived long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid are well established. Less studied are specific effects of individual long-chain polyunsaturated fatty acids. Based on data from 16 published clinical trials, this review examines effects of DHA triglyceride (TG) oil derived from algae (algal-DHA) on serum TG levels and related parameters. Study populations included subjects with both normal and elevated TG levels including those with persistent hypertriglyceridemia treated with concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. At doses of 1-2 g/d, algal-DHA significantly lowered plasma TG levels (up to 26%) either administered alone or in combination with statins. The reduction in TG levels was markedly greater in hypertriglyceridemic than in normal subjects. Algal-DHA modestly increased plasma levels of both high-density lipoprotein and low-density lipoprotein cholesterol. The increased plasma level of low-density lipoprotein cholesterol was associated with a shift of lipoprotein particle size toward larger, less atherogenic subfractions. In some subjects, blood pressure and heart rate were significantly reduced. Algal-DHA was safe and well tolerated. Unlike fish oil, algal-DHA seldom caused gastrointestinal complaints such as fishy taste and eructation, attributes of importance for patient compliance in high-dose therapy. Regression analysis that showed a linear relationship between baseline TG and magnitude of TG reduction suggests that a study of patients with very high TG levels (>500 mg/dL) is warranted. Future pharmacologic therapies for treating hypertriglyceridemia may include algal-DHA.
FISH analysis for chromosomes 13, 16, 18, 21, 22, X and Y in all blastomeres of IVF pre-embryos from 144 randomly selected donated human oocytes and impact on pre-embryo morphology (2003)

The data demonstrate the high degree of genetic heterogeneity in a randomly selected pool of donated pre-embryos from an IVF programme. Further, we found that uniformity of blastomere size, degree of fragmentation and cleavage kinetics reflect the cytogenetic status of the pre-embryo and are therefore important in the selection of pre-embryos.
Cloning and Expression of the Chicken Interferon-γ Gene (1995)

We have cloned the gene for chicken interferon-gamma (ChIFN-gamma) from a cDNA expression library generated from a T cell line (CC8.1h) that produces high levels of IFN-gamma activity. CC8.1h constitutively produces IFN activity that shares physiochemical properties with mammalian IFN-gamma. ChIFN-gamma, when secreted by CC8.1h or expressed in transfected COS cells, is heat labile, inactivated by exposure to pH 2, and capable of inducing nitrite production by chicken macrophages. These properties clearly distinguish it from chicken and mammalian type I IFN. The ChIFN-gamma gene codes for a predicted mature protein of 145 amino acids with a molecular mass of 16.8 kD. There are two potential N-glycosylation sites located near the N terminus. ChIFN-gamma protein shares significant amino acid homology with mammalian IFN-gamma proteins; in particular it also contains the highly conserved motifs that are present in all mammalian IFN-gamma proteins. ChIFN-gamma is 35 and 32% identical to the equine and human counterparts, respectively, but shares only 15% homology with chicken type I IFN. These findings show that the emergence of the two principal types of IFN predates the divergence of avians and mammals that occurred some 350 million years ago.
Highly deacetylated chitosan and its properties (1983)

Abstract A preparative method has been established for obtaining chitosan products which have a desired degree of deacetylation of up to virtually 100%. Effective deacetylation was attained by intermitently washing the intermediate product in water two or more times during the alkali treatment. The weight average molecular weight ( M̄ w ) of the product, which was measured by gel permeation liquid chromatography, was about 5 × 10 5 at the highest deacetylation of nearly 100%, and the degradation of the molecular chain was not so significant. Tensile strength of the wet film increased markedly with increasing degree of deacetylation, while the dry film did not show a corresponding significant increase of the tensile strength. In the infrared spectra of chitosan film new sharp bands appeared especially at the high degree of deacetylation. This was attributed to increased “crystallization” brought about by high deacetylation.
Treatment of metastatic melanoma: an overview. (2009)

The 10-year survival rate for patients with metastatic melanoma is less than 10%. Although surgery and radiation therapy have a role in the treatment of metastatic disease, systemic therapy is the mainstay of treatment for most patients. Single-agent chemotherapy is well tolerated but is associated with response rates of only 5% to 20%. Combination chemotherapy and biochemotherapy may improve objective response rates but do not extend survival and are associated with greater toxicity. Immunotherapeutic approaches such as high-dose interleukin-2 are associated with durable responses in a small percentage of patients. In this article, we review the treatments for metastatic melanoma including promising investigational approaches.
Molecular Cloning and Characterization of Human Podocalyxin-like Protein (1997)

Human renal cortex and heart cDNA libraries were screened for a human homolog of rabbit PCLP1 using the rabbit PCLP1 cDNA as a probe. Clones spanning 5869 base pairs with an open reading frame coding for a 528-amino acid peptide were obtained. The putative peptide contains a potential signal peptide and a single membrane-spanning region. The extracellular domain contains multiple potential sites for N- and O-linked glycosylation and 4 cysteines for potential disulfide bonding similar to rabbit PCLP1. On Northern blot a major transcript is seen at 5.9 kilobases. Antibodies to this protein show a doublet at 160/165 kDa on Western blots of human glomerular extract and a pattern of intense glomerular staining and vascular endothelial staining on immunofluorescence of human kidney sections. Comparison of the rabbit and human peptide sequences shows a high degree of identity in the transmembrane and intracellular domains (96%) with a lower degree of identity in the extracellular domain (36%). An antibody to the intracellular domain reacted across species (human, rabbit, and rat) and recognized both rabbit PCLP1 and rat podocalyxin. An interspecies Southern blot probed with a cDNA coding for the intracellular domain showed strong hybridization to all vertebrates tested in a pattern suggesting a single copy gene. We conclude that this cDNA and putative peptide represent the human homolog of rabbit PCLP1 and rat podocalyxin.
NAS switch: a novel CIFS server virtualization (2003)

This paper proposes a common Internet file system (CIFS) server virtualization method which requires no proprietary software or hardware for clients or network attached storage (NAS) units. The method is implemented as an in-band network application between clients and NAS units, and it provides users and administrators with a single virtual NAS system that incorporates all their units. Since almost all name resolution operations are performed by individual NAS units independently, use of this method imposes only a very light computational load and creates little latency.
tRFdb: a database for transfer RNA fragments (2014)

We have created tRFdb, the first database of transfer RNA fragments (tRFs), available at http://genome.bioch.virginia.edu/trfdb/. With over 100 small RNA libraries analyzed, the database currently contains the sequences and read counts of the three classes of tRFs for eight species: R. sphaeroides, S. pombe, D. melanogaster, C. elegans, Xenopus, zebra fish, mouse and human, for a total of 12,877 tRFs. The database can be searched by tRF ID or tRF sequence, and the results can be limited by organism. The search results show the genome coordinates and names of the tRNAs the sequence may derive from, and there are links for the sequence of the tRF and parental tRNA, and links for the read counts in all the corresponding small RNA libraries. As a case study for how this database may be used, we have shown that a certain class of tRFs, tRF-1s, is highly upregulated in B-cell malignancies.
MHCflurry 2.0: Improved Pan-Allele Prediction of MHC Class I-Presented Peptides by Incorporating Antigen Processing (2020)

Computational prediction of the peptides presented on major histocompatibility complex (MHC) class I proteins is an important tool for studying T cell immunity. The data available to develop such predictors have expanded with the use of mass spectrometry to identify naturally presented MHC ligands. In addition to elucidating binding motifs, the identified ligands also reflect the antigen processing steps that occur prior to MHC binding. Here, we developed an integrated predictor of MHC class I presentation that combines new models for MHC class I binding and antigen processing. Considering only peptides first predicted by the binding model to bind strongly to MHC, the antigen processing model is trained to discriminate published mass spectrometry-identified MHC class I ligands from unobserved peptides. The integrated model outperformed the two individual components as well as NetMHCpan 4.0 and MixMHCpred 2.0.2 on held-out mass spectrometry experiments. Our predictors are implemented in the open source MHCflurry package, version 2.0 (github.com/openvax/mhcflurry).
Near field focusing by edge diffraction (2018)

Spherical microparticles have the ability for nonresonant focusing of light in the near field zone, forming nanojet (NJ) beams. Arbitrary-shaped microstructures, with wavelength-scale dimensions, may offer similar functionality with lower fabrication complexity. The focusing properties are ruled by the edge diffraction phenomenon. The diffraction of light on the edge of a dielectric microstructure forms a tilted focused beam whose deviation angle depends on the index ratio between the structure material and host medium. The beam geometry and field intensity enhancement can be tuned by varying the curvature of the edge line. Interference of edge diffracted waves from different segments of the edge line creates a condensed beam in the near field zone, the photonic nanojet.
Resonant loss for helix traveling wave tubes (1977)

This paper describes a scheme for suppressing backward wave oscillations (BWO) in high-power, PPM focused helix traveling wave tubes. The scheme consists of lossy, resonant meander lines deposited on each of the helix support rods and located between each helix turn By varying the length of the line, it can be made to resonate at the helix circuit's π-mode frequency. In this way the "resonator" provides loss in the vicinity of the π-mode, thereby inhibiting backward wave interaction. Test results have shown at least a four-fold increase in the BWO start current for a tube employing this resonant loss scheme.
The Baeyer-Villiger Oxidation of Ketones Using HMS Supported Peroxycarboxylic Acids (2000)

Hexagonal Mesoporous Silica (HMS) supported peroxycarboxylic acids are efficient reagents in the Baeyer-Villiger oxidation of cyclic and linear ketones to lactones and esters respectively at room temperature in hexane.
Debaryomyces hansenii — an extremophilic yeast with biotechnological potential (2006)

We illuminate the ecological, physiological and genetic characteristics of the yeast Debaryomyces hansenii in the view of our belief that this metabolically versatile, non-pathogenic, osmotolerant and oleaginous microorganism represents an attractive target for fundamental and applied biotechnological research. To this end, we give a broad overview of extant biotechnological procedures using D. hansenii, e.g. in the manufacture of various foods, and propose research into the heterologous synthesis of a range of fine chemicals.
Arginyl-glycyl-aspartic acid sequences and fibrinogen binding to platelets (1987)

Human fibrinogen has an Arg-Gly-Asp-Ser (RGDS) sequence at residues 572- 575 of its A alpha-chain. Although RGDS-containing peptides inhibit fibrinogen binding to stimulated platelets, these peptides also inhibit platelet binding of human fibrinogen fragment X and rat fibrinogen, which lack RGDS sequences corresponding to A alpha 572–575. Thus competition between free RGD-containing peptides and internal RGDS sequence at A alpha 572–575 is not the basis for their inhibition of fibrinogen binding to platelets. Addition of a Thr to the carboxy- terminus and an Asn to the amino-terminus of the RGDS sequence, the amino acids corresponding to A alpha 576 and 571 respectively, reduced the inhibitory potency of RGDS-containing peptides by fourfold to tenfold. Arg-Gly-Asp-Phe (RGDF) corresponds to A alpha 95–98, and the RGDF peptide was an effective inhibitor of fibrinogen binding, fourfold to fivefold more potent than RGDS. Thus, local primary structure may play an important role in regulating the capacity of RGD sequences in proteins to interact with specific adhesion receptors.
Mood-based navigation through large collections of musical data (2005)

The last years have seen a remarkable reduction of cost and size of mass storage devices, like hard disks and flash memory. There is no technological barrier any longer that prevents a user to have several thousand of different music titles stored on his or her mobile device. This calls for new mechanisms that allow users to explore large musical databases. Additionally, mobile 'mp3' players today have the size of a stripe of chewing gum, which gives rise to a yet another problem: how to select a song from a large collection if there is no keyboard and only very little graphical output available? In this paper, a mood-based song selection and exploration scheme is proposed, in which the user selects the desired mood of a song in a two-dimensional mood plane. An algorithm that can automatically determine the mood of a music piece is described. An evaluation on a small music collection of 400 music pieces shows the viability of the new approach.
L-Phenylalanine Production by Analog-resistant Mutants of Corynebacterium glutamicum (1974)

Mutants resistant to phenylalanine- or tyrosine-analogs were isolated from a wild type strain of Corynebacterium glutamicum ATCC 13032 and a tyrosine auxotroph TL-3 by mutagenic treatment with N-methyl-N’-nitro-N-nitroso guanidine (NTG) and screened for l-phenylalanine production. The growth of C. glutamicum ATCC 13032 was strongly inhibited by a phenylalanine analog, p-fluorophenylalanine (PFP), at a concentration of 1 mg/ml. C. glutamicum TL-3 was inhibited by PFP and another phenylalanine analog, β-2-thienylalanine (TA), at a concentration of 50 μg/ml and 400 μg/ml respectively. A prototrophic mutant resistant to PFP (4 mg/ml) produced l-phenylalanine at a concentration of 5.5 mg/ml and a trace amount of l-tyrosine in a cane molasses medium containing 10% of sugar calculated as glucose. A tyrosine auxotrophic mutant resistant to PFP (100 μg/ml) and p-aminophenyl-alanine (PAP) (1 mg/ml), 31–PAP–20–22, produced L-phenylalanine at a concentration of 9.5 mg/ml in the molasses medium. l-Phenylalanine production in these mutants was inhibited by l-tyrosine and stimulated by l-tryptophan.
Lack of therapeutic efficacy of an antibody to α 4 β 7 in SIVmac251-infected rhesus macaques (2019)

Sustained virologic control of human immunodeficiency virus type 1 (HIV-1) infection after discontinuation of antiretroviral therapy (ART) is a major goal of the HIV-1 cure field. A recent study reported that administration of an antibody against α<sub>4</sub>β<sub>7</sub> induced durable virologic control after ART discontinuation in 100% of rhesus macaques infected with an attenuated strain of simian immunodeficiency virus (SIV) containing a stop codon in <i>nef</i> We performed similar studies in 50 rhesus macaques infected with wild-type, pathogenic SIVmac251. In animals that initiated ART during either acute or chronic infection, anti-α<sub>4</sub>β<sub>7</sub> antibody infusion had no detectable effect on the viral reservoir or viral rebound after ART discontinuation. These data demonstrate that anti-α<sub>4</sub>β<sub>7</sub> antibody administration did not provide therapeutic efficacy in the model of pathogenic SIVmac251 infection of rhesus macaques.
Erratum: Structural Principles and Amorphouslike Thermal Conductivity of Na-Doped Si Clathrates [Phys. Rev. Lett. 85, 114 (2000)] (2001)

In this Letter, we reported the thermal conductivity ͑k͒ of Na 8 Si 46 .Inadvertently, we had not corrected the data for the coefficient of contact thermal conductivity [1].When this is accounted for, the thermal conductivity is higher than reported in the Letter.Correct results are shown in Fig. 1.These results agree well with recent steady-state measurements for a pressed pellet of Na 8 Si 46 [2].The main conclusions of the Letter concerning structural principles of this clathrate remain the same, and the thermal conductivity is still amorphouslike (much smaller than for crystalline Si, and with a different temperature dependence).FIG. 1. Thermal conductivity for Na 8 S 46 .The error bars indicate typical experimental uncertainty.We are grateful to G. Nolas for useful discussions.
Targeted Next-Generation Sequencing Panel (ThyroSeq) for Detection of Mutations in Thyroid Cancer (2013)

The ThyroSeq NGS panel allows simultaneous testing for multiple mutations with high accuracy and sensitivity, requires a small amount of DNA and can be performed in a variety of thyroid tissue and fine-needle aspiration samples, and provides quantitative assessment of mutant alleles. Using this approach, the point mutations were detected in 30%-83% of specific types of thyroid cancer and in only 6% of benign thyroid nodules and were shown to be present in the majority of cells within the cancer nodule.
Therapeutic Potential of Metabotropic Glutamate Receptor Modulators (2012)

Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS) and is a major player in complex brain functions. Glutamatergic transmission is primarily mediated by ionotropic glutamate receptors, which include NMDA, AMPA and kainate receptors. However, glutamate exerts modulatory actions through a family of metabotropic G-protein-coupled glutamate receptors (mGluRs). Dysfunctions of glutamatergic neurotransmission have been implicated in the etiology of several diseases. Therefore, pharmacological modulation of ionotropic glutamate receptors has been widely investigated as a potential therapeutic strategy for the treatment of several disorders associated with glutamatergic dysfunction. However, blockade of ionotropic glutamate receptors might be accompanied by severe side effects due to their vital role in many important physiological functions. A different strategy aimed at pharmacologically interfering with mGluR function has recently gained interest. Many subtype selective agonists and antagonists have been identified and widely used in preclinical studies as an attempt to elucidate the role of specific mGluRs subtypes in glutamatergic transmission. These studies have allowed linkage between specific subtypes and various physiological functions and more importantly to pathological states. This article reviews the currently available knowledge regarding the therapeutic potential of targeting mGluRs in the treatment of several CNS disorders, including schizophrenia, addiction, major depressive disorder and anxiety, Fragile X Syndrome, Parkinson's disease, Alzheimer's disease and pain.