gebhart/patrepeval huggingface dataset:
Size Restriction on Peptide Utilization in Escherichia coli (1968)

It has been shown by measuring the growth response of appropriate amino acid auxotrophs to several series of homologous oligopeptides that higher oligomers were unable to enter Escherichia coli. The exclusion did not always occur at the same chain length of peptide, for the oligomer at which exclusion was first observed varied with the nature of the amino acid residues. To investigate the possibility that over-all size may be important in regulating peptide entry, the relative hydrodynamic volumes of the peptides used in the above studies were measured by gel filtration on Sephadex G-15. These studies suggested that to be able to enter E. coli the hydrodynamic volume of a peptide could not exceed a certain critical value. To test the generality of this observation, the heterogeneous mixture of peptides present in the enzymatic protein hydrolysate Neopeptone was separated according to size on Sephadex G-15. On the basis of the previous measurements it proved possible to exactly predict which of the Neopeptone peptide fractions could enter the cell and which would be excluded. Lack of competition between peptides that can enter and peptides that are excluded, suggests that the exclusion may occur external to the peptide transport system. The speculation is raised that the cell wall may act as a molecular sieve preventing molecules above a certain size from crossing the cell envelope, the critical hydrodynamic volume being some measure of the pore size of such a sieve.
Effectiveness of a graphical display of retrieval results (1997)

We present the design of a visualization tool that graphically displays the strength of query concepts in the retrieved documents. Graphically displaying document surrogate information enables set-at-a-time perusal of documents, rather than document-at-a-time perusal of textual displays. By prvialing additional relevance information about the retrieved documents, the tool aids the user in accurately identifying relevant documents. Results of an experiment evaluating the tool shows that when users have the tool they are able to identify relevant documents in a shorter period of time than without the tool, and with increased accuracy. We have evidence to believe that appropriately designed graphical displays can enable users to better interact with the system.
Prevention of Recurrence of IDDM in Islet-Transplanted Diabetic NOD Mice by Adjuvant Immunotherapy (1992)

Insulin-dependent diabetes mellitus (IDDM) involves the destruction of the insulin-producing cells in the islets of Langerhans. One possible cure is by transplanting the islet cells; however, transplanted islets, even between identical twins, are subject to autoimmune destruction by the disease process, resulting in diabetes recurrence. We recently reported that complete Freund's adjuvant (CFA), an immunomodulating agent, prevented development of autoimmune diabetes in the NOD mouse. In this study, we evaluated adjuvant therapy in prevention of autoimmune destruction and rejection of transplanted islets in diabetic NOD mice. After transplantation, untreated syngeneic islet recipients (n = 16) initially became normoglycemic and then hyperglycemic, with a median survival time (MST) of the graft of 17 days. When CFA was administered at the time of transplantation, 11 of 13 CFA-treated syngeneic islet recipients remained normoglycemic long term (greater than 100 days) with an MST greater than 107 days. Ten of 11 mice maintained indefinite normoglycemia until the conclusion of follow-up (101 to 172 days). When adjuvant therapy was used in conjunction with allogeneic islet transplantation, graft survival was not extended, with MST being similar to the untreated allogeneic islet recipients (12 [n = 5] and 13 [n = 5] days, respectively). The extended acceptance of second syngeneic islet grafts by CFA-treated mice indicates that the persistent autoimmunity against the transplanted islets can be reversed in the diabetic NOD mice after CFA treatment.
Lipid-Modifying Enzymes in Human Tear Fluid and Corneal Epithelial Stress Response (2013)

Extracellular stress affects tear fluid composition more profoundly than just secretion of proinflammatory mediators. Lipids at the ocular surface, either in tear fluid or within the corneal epithelial cells, can be modified by a relatively large array of lipases to modulate their functions. Moreover, extracellular vesicles in the tear fluid could represent a valuable noninvasive diagnosis tool for anterior segment diseases.
Heat Shock Factor 1 Mediates Hemin-induced hsp70 Gene Transcription in K562 Erythroleukemia Cells (1998)

Transcriptional induction of the hsp70 gene is mediated by heat shock factor 1 (HSF1) rapidly activated upon heat and other stresses. HSF2 has been thought to be responsible for accumulation of HSP70 during hemin-induced differentiation of human K562 erythroleukemia cells because of accompanying acquisition of HSF2 DNA binding activity. However, there has not been any direct evidence for such a functional role of HSF2. The purpose of this study is to clarify the roles of HSF1 and HSF2 in HSP70 induction in hemin-treated K562 cells. We show here that a chimeric polypeptide of HSF2 and GAL4 DNA binding domain (GAL4-BD-HSF2) was unable to induce a GAL4 binding site-containing luciferase reporter gene in response to hemin and that exogenously overproduced HSF2 also failed to increase expression of a heat shock element-containing reporter. On the contrary, expression of a GAL4-BD-HSF1 chimeric protein responded to hemin treatment as well as to heat shock, and transiently overexpressed HSF1 caused hemin-responsive induction of the reporter gene in a dose-dependent manner. These results indicate that HSF1, rather than HSF2, primarily mediates the hemin-induced transcription of the hsp70 gene.
De novo assembly using low-coverage short read sequence data from the rice pathogen Pseudomonas syringae pv. oryzae (2008)

We developed a novel approach for de novo genome assembly using only sequence data from high-throughput short read sequencing technologies. By combining data generated from 454 Life Sciences (Roche) and Illumina (formerly known as Solexa sequencing) sequencing platforms, we reliably assembled genomes into large scaffolds at a fraction of the traditional cost and without use of a reference sequence. We applied this method to two isolates of the phytopathogenic bacteria Pseudomonas syringae. Sequencing and reassembly of the well-studied tomato and Arabidopsis pathogen, Pto(DC3000), facilitated development and testing of our method. Sequencing of a distantly related rice pathogen, Por(1_)(6), demonstrated our method's efficacy for de novo assembly of novel genomes. Our assembly of Por(1_6) yielded an N50 scaffold size of 531,821 bp with >75% of the predicted genome covered by scaffolds over 100,000 bp. One of the critical phenotypic differences between strains of P. syringae is the range of plant hosts they infect. This is largely determined by their complement of type III effector proteins. The genome of Por(1_6) is the first sequenced for a P. syringae isolate that is a pathogen of monocots, and, as might be predicted, its complement of type III effectors differs substantially from the previously sequenced isolates of this species. The genome of Por(1_6) helps to define an expansion of the P. syringae pan-genome, a corresponding contraction of the core genome, and a further diversification of the type III effector complement for this important plant pathogen species.
A comprehensively molecular haplotype-resolved genome of a European individual (2011)

Independent determination of both haplotype sequences of an individual genome is essential to relate genetic variation to genome function, phenotype, and disease. To address the importance of phase, we have generated the most complete haplotype-resolved genome to date, "Max Planck One" (MP1), by fosmid pool-based next generation sequencing. Virtually all SNPs (>99%) and 80,000 indels were phased into haploid sequences of up to 6.3 Mb (N50 ~1 Mb). The completeness of phasing allowed determination of the concrete molecular haplotype pairs for the vast majority of genes (81%) including potential regulatory sequences, of which >90% were found to be constituted by two different molecular forms. A subset of 159 genes with potentially severe mutations in either cis or trans configurations exemplified in particular the role of phase for gene function, disease, and clinical interpretation of personal genomes (e.g., BRCA1). Extended genomic regions harboring manifold combinations of physically and/or functionally related genes and regulatory elements were resolved into their underlying "haploid landscapes," which may define the functional genome. Moreover, the majority of genes and functional sequences were found to contain individual or rare SNPs, which cannot be phased from population data alone, emphasizing the importance of molecular phasing for characterizing a genome in its molecular individuality. Our work provides the foundation to understand that the distinction of molecular haplotypes is essential to resolve the (inherently individual) biology of genes, genomes, and disease, establishing a reference point for "phase-sensitive" personal genomics. MP1's annotated haploid genomes are available as a public resource.
Functionalization of Acetylene-Terminated Monolayers on Si(100) Surfaces:  A Click Chemistry Approach (2007)

In this article, we report the functionalization of alkyne-terminated alkyl monolayers on Si(100) using "click" chemistry, specifically, the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of azides with surface-bound alkynes. Covalently immobilized, structurally well-defined acetylene-terminated organic monolayers were prepared from a commercially available terminal diyne species using a one-step hydrosilylation procedure. Subsequent derivatization of the alkyne-terminated monolayers in aqueous environments with representative azide species via a selective, reliable, robust cycloaddition process afforded disubstituted surface-bound [1,2,3]-triazole species. Neither activation procedures nor protection/deprotection steps were required, as is the case with more established grafting approaches for silicon surfaces. Detailed characterization using X-ray photoelectron spectroscopy and X-ray reflectometry demonstrated that the surface acetylenes had reacted in moderate to high yield to give surfaces exposing alkyl chains, oligoether anti-fouling moieties, and functionalized aromatic structures. These results demonstrate that click immobilization offers a versatile, experimentally simple, chemically unambiguous modular approach to producing modified silicon surfaces with organic functionality for applications as diverse as biosensors and molecular electronics.
A combined magnetic sector–time‐of‐flight mass spectrometer for structural determination studies by tandem mass spectrometry (1995)

Abstract A combined magnetic sector–time‐of‐flight instrument has been constructed and used with both continuous (liquid secondary ion mass spectrometry and electrospray ionization) and pulsed (matrix‐assisted laser desorption/ionization) ion sources. The design includes provision for both low‐ and high‐energy gas collision induced decompositions and orthogonal acceleration of the product ions into the time‐of‐flight mass analyser. Tandem mass spectra may be acquired for singly and multiply charged precursor ions and reliable mass measurements are easily obtained. Product‐ion mass spectra are quite reproducible regardless of any instability in the precursor ion beam intensity.
Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize ra patients with fibromyalgia. (2004)

FM exists in a substantial number of patients with RA (17.1%), who have more severe RA by subjective and objective measures, greater medical costs, worse outcomes, more comorbidities, sociodemographic disadvantage, and substantially worse quality of life. We hypothesize that illness severity and sociodemographic disadvantage both play a role in producing the clinical picture of FM.
A scaling normalization method for differential expression analysis of RNA-seq data (2010)

The fine detail provided by sequencing-based transcriptome surveys suggests that RNA-seq is likely to become the platform of choice for interrogating steady state RNA. In order to discover biologically important changes in expression, we show that normalization continues to be an essential step in the analysis. We outline a simple and effective method for performing normalization and show dramatically improved results for inferring differential expression in simulated and publicly available data sets.
GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment (2003)

Previous studies have shown that the multiple myeloma (MM) cell line and MM patient cells express high-affinity vascular endothelial growth factor (VEGF) receptor-1 or Fms-like tyrosine kinase-1 (Flt-1) but not VEGF receptor-2 or Flk-1/kinase insert domain-containing receptor (Flk-1/KDR) and that VEGF triggers MM cell proliferation through a mitogen-activated protein kinase (MAPK)-dependent pathway and migration through a protein kinase C (PKC)-dependent pathway. The present study evaluates the efficacy of the small molecule tyrosine-kinase inhibitor GW654652, which inhibits all 3 VEGF receptors with similar potency. We show that GW654652 acts directly on MM cells and in the bone marrow microenvironment. Specifically, GW654652 (1-10 microg/mL) inhibits, in a dose-dependent fashion, VEGF-triggered migrational activity and cell proliferation of MM cell lines that are sensitive and resistant to conventional therapy. As expected from our previous studies of VEGF-induced signaling and sequelae in MM cells, GW654652 blocked VEGF-induced Flt-1 phosphorylation and downstream activation of AKT-1 and MAPK-signaling cascades. Importantly, GW654652 also inhibits interleukin-6 and VEGF secretion and proliferation of MM cells induced by tumor cell binding to bone marrow (BM) stromal cells. The activity of a pan-VEGF receptor inhibitor against MM cells in the BM milieu, coupled with its lack of major toxicity in preclinical mouse models, provides the framework for clinical trials of this drug class to improve patient outcome in MM.
Purification of colony-stimulating factor by affinity chromatography (1982)

Studies were undertaken to determine whether L-cell-derived colony-stimulating factor (CSF) could be purified by a single step affinity chromatographic technique. A quantity of 100 X 10(6) units of purified anti-CSF was coupled to cyanogen bromide activated Sepharose 4B; colony assays revealed complete binding of the antibodies to the gel. Three 10- liter pools of serum-free L-cell CSF were concentrated by ultrafiltration, applied to the gel, and eluted with a low pH, high molarity buffer. Recovery of CSF ranged from 68%-100% with greater than 1000-fold decreases in protein content. Specific activity of the purified CSF ranged from 2.8 to 5.9 X 10(7) U of CSF/mg protein. Following iodination, each purified pool of CSF revealed a major 63,000- dalton peak of radioactivity that comigrated with CSF activity in SDS- acrylamide gels. In addition, several smaller peaks of 50,000 and 40,000 molecular weight were also detected. Approximately two-thirds of the purified CSF was adherent to concanavalin-A with elution by a competing sugar. Electrophoretic mobility was retarded by incubation with neuraminidase. These chromatographic studies confirm the observation that CSF is a glycoprotein but also suggest variable degrees of glycosylation of the molecule. This chromatographic technique should prove useful in the rapid purification of large quantities of CSF for physiologic and biochemical characterization.
Peptide Antagonist of the Androgen Receptor (2010)

Androgen receptor (AR) is a steroid hormone receptor that is activated by endogenous androgens, mainly testosterone and 5alpha-dihydrotestosterone (5alpha-DHT). AR is also an important drug target, and AR antagonists (antiandrogens) have been widely used for prostate cancer therapy. Antiandrogens currently available on the market are all small molecules that antagonize AR function via binding to the ligand binding domain (LBD). AR peptide antagonist has been proposed as a 'mechanism-based' approach to directly block AR function by interrupting AR-protein interactions from the surface of the receptor. Without targeting the rigid ligand binding pocket within LBD, peptide antagonists allow more flexibility in structure design, and are likely to provide more efficient and complete blockade of AR function as compared to small molecule antagonists. AR interacts with a variety of proteins, and the interaction may be mediated by different functional domains of the receptor. Although varieties of AR-protein interfaces might serve as the target for peptide antagonist, majority of ongoing research is still focusing on peptides that target the LBD, which is mainly due to the abundance of structural information revealed by crystal structures. This review gives an overview of the current research attempts to develop AR peptide antagonists, particularly peptide antagonists that target the LBD and N-terminal domain (NTD). The challenges and opportunities for future discovery and development of peptide antagonists are discussed as well.
Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans (2005)

Specific germline activating point mutations in the gene encoding the tyrosine kinase receptor FGFR3 (fibroblast growth factor receptor 3) result in autosomal dominant human skeletal dysplasias. The identification in multiple myeloma and in two epithelial cancers-bladder and cervical carcinomas-of somatic FGFR3 mutations identical to the germinal activating mutations found in skeletal dysplasias, together with functional studies, have suggested an oncogenic role for this receptor. Although acanthosis nigricans, a benign skin tumor, has been found in some syndromes associated with germinal activating mutations of FGFR3, the role of activated FGFR3 in the epidermis has never been investigated. Here, we targeted an activated receptor mutant (S249C FGFR3) to the basal cells of the epidermis of transgenic mice. Mice expressing the transgene developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis, one of the most common benign epidermal tumors in humans. We therefore screened a series of 62 cases of seborrheic keratosis for FGFR3 mutations. A large proportion of these tumors (39%) harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms. Our findings directly implicate FGFR3 activation as a major cause of benign epidermal tumors in humans.
The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons (1995)

The characteristics and mechanisms of synchronized firing in developing networks of cultured cortical neurons were studied using multisite recording through planar electrode arrays (PEAs). With maturation of the network (from 3 to 40 d after plating), the frequency and propagation velocity of bursts increased markedly (approximately from 0.01 to 0.5 Hz and from 5 to 100 mm/sec, respectively), and the sensitivity to extracellular magnesium concentration (0-10 mM) decreased. The source of spontaneous bursts, estimated from the relative delay of onset of activity between electrodes, varied randomly with each burst. Physical separation of synchronously bursting networks into several parts using an ultraviolet laser, divided synchronous bursting into different frequencies and phases in each part. Focal stimulation through the PEA was effective at multiple sites in eliciting bursts, which propagated over the network from the site of stimulation. Stimulated bursts exhibited both an absolute refractory period and a relative refractory period, in which partially propagating bursts could be elicited. Periodic electrical stimulation (at 1 to 30 sec intervals) produced slower propagation velocities and smaller numbers of spikes per burst at shorter stimulation intervals. These results suggest that the generation and propagation of spontaneous synchronous bursts in cultured cortical neurons is governed by the level of spontaneous presynaptic firing, by the degree of connectivity of the network, and by a distributed balance between excitation and recovery processes.
New Directions for the Photocatalytic Reduction of CO2: Supramolecular, scCO2 or Biphasic Ionic Liquid−scCO2 Systems (2010)

There is an urgent need for the discovery of carbon-neutral sources of energy to avoid the consequences of global warming caused by ever-increasing atmospheric CO2 levels. An attractive possibility is to use CO2 captured from industrial emissions as a feedstock for the production of useful fuels and precursors such as carbon monoxide and methanol. An active field of research to achieve this goal is the development of catalysts capable of harnessing solar energy for use in artificial photosynthetic processes for CO2 reduction. Transition-metal complexes are excellent candidates, and it has already been shown that they can be used to reduce CO2 with high quantum efficiency. However, they generally suffer from poor visible light absorption, short catalyst lifetimes, and poor reaction rates. In this Perspective, the field of photocatalytic CO2 reduction is introduced, and recent developments that seek to improve the efficiency of such catalytic processes are highlighted, especially CO2 reduction with supramolecules and molecular systems in supercritical CO2 (scCO2) or biphasic ionic liquid−scCO2 mixtures.
Editorial: Advances in Combination Tumor Immunotherapy (2015)

EDITORIAL article Front. Oncol., 22 September 2015Sec. Cancer Immunity and Immunotherapy Volume 5 - 2015 | https://doi.org/10.3389/fonc.2015.00198
Organic Thin Film Transistors on Flexible Polyimide Substrates Fabricated by Full Wafer Stencil Lithography (2009)

This paper presents new results on miniaturized organic thin film transistors (TFT) fabricated on a spin coated polyimide (PI) film. Patterning steps, that are vital for the integrity and electrical performances of the organic TFT, were performed using resistless shadow-mask lithography with two high precision MEMS fabricated stencils, thus avoiding solvents and high temperature processes. Both pentacene and source-drain (S/D) electrodes were directly patterned through stencils with high accuracy on wafer scale. The TFT have been characterized before and after peeling the flexible PI film off the rigid surface, showing full transistor functionality in both cases.
Ein photochemisch „schaltbarer” Kronenether mit intraanularem 4‐Methoxyphenylazo‐Substituenten (1985)

Die Bindung von Metallionen verhindern kann der intraanulare 4‐Methoxyphenylazo‐Substituent in einem Dibenzo[18]krone‐6‐Analogon, in welchem eine CH 2 OCH 2 ‐Gruppierung durch einen (substituierten) m ‐Phenylenring ersetzt ist. Wird der Substituent photochemisch herausgeklappt, so werden Metallionen in der für Kronenether typischen Weise komplexiert.