gebhart/patrepeval huggingface dataset:
Targeting the “Cytokine Storm” for Therapeutic Benefit (2013)

ABSTRACT Inflammation is the body's first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis , do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.
Many ways to make an influenza virus - review of influenza virus reverse genetics methods (2012)

Methods to introduce targeted mutations into a genome or, in the context of virology, into a virus are subsumed under the term reverse genetics (RG). Influenza viruses are important human pathogens that continue to surprise us. The development of RG for influenza viruses has greatly expanded our knowledge about influenza virus and enabled researchers to generate influenza viruses with rationally designed genotypes. Currently, a wide array of influenza virus RG methods is available. These can all be traced to fundamental principles essential in any RG system for negative-strand RNA viruses. This review gives an overview of these principles and of the multitude of RG methods, categorising them by technical characteristics.
On the Chirality of Self‐Assembled DNA Octahedra (2009)

Was spricht gegen windschief? Ein rationaler Ansatz ermöglichte es, die Selbstorganisation eines DNA-Oktaeders zu programmieren (siehe Struktur; der Farbgradient deutet den Abstand vom Oktaederzentrum an). Eine genaue Strukturuntersuchung ergab, dass die Assoziation der Nanoobjekte stereoselektiv war (die Ansicht einer Ecke zeigt den schiefen Hohlraum, der die Bestimmung der Chiralität der Oktaeder ermöglichte).
Investigating pulsed dye laser-blood vessel interaction with color Doppler optical coherence tomography (1998)

A non-invasive method of imaging laser irradiated blood vessels has been achieved using Color Doppler Optical Coherence Tomography (CDOCT). This method may increase understanding of the mechanisms behind treatment of vascular disorders. The CDOCT system used a 1280 nm center wavelength superluminescent diode. A 585 nm, 360 aes pulsed dye laser was used to irradiate hamster dorsal skin flap window preparations. Irradiation sites were imaged with CDOCT prior to, immediately after, and 24 hours after laser irradiation. The processed CDOCT signal provided an estimate of the blood flow velocity. An increase in the blood vessel backscattered signal was observed as blood or vessel walls were coagulated. A decrease in damaged blood vessel reflectivity occurred after twenty four hours.
MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury (2016)

Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency. In vivo experiments in the zebrafish model demonstrated that the tubulus cells of the larvae undergo cell death after the knockdown of mdm2. Doxycycline-induced deletion of MDM2 in tubular cell-specific MDM2-knockout mice Pax8rtTa-cre; MDM2f/f caused acute kidney injury with increased plasma creatinine and blood urea nitrogen and sharp decline of glomerular filtration rate. Histological analysis showed massive swelling of renal tubular cells and later their loss and extensive tubular dilation, markedly in proximal tubules. Ultrastructural changes of tubular epithelial cells included swelling of the cytoplasm and mitochondria with the loss of cristae and their transformation in the vacuoles. The pathological phenotype of the tubular cell-specific MDM2-knockout mouse model was completely rescued by co-deletion of p53. Tubular epithelium compensates only partially for the cell loss caused by MDM2 depletion by proliferation of surviving tubular cells, with incomplete MDM2 deletion, but rather mesenchymal healing occurs. We conclude that MDM2 is a non-redundant survival factor for proximal tubular cells by protecting them from spontaneous p53 overexpression-related cell death.
Searching for Eastern's Bottom Line (1984)

[Excerpt] Over the last two years labor unions have faced escalating demands for concessions and give-backs. To counter the spread of concession fever, many unions are trying to develop a more sophisticated picture of a company's financial condition and overall strategy. First and foremost they are taking a closer look at the factors that determine a company's bottom line. The underlying assumption is that management uses financial accounting gimmicks to "reduce" profits and justify concessions. This is not an easy task, primarily because the expertise and data needed to investigate a company's performance is not readily available to most unions, especially at the regional or local level. In-house capacity in this area usually resides at the national level where in-depth research on specific companies is either inaccessible or nonexistent. Very few accounting, consulting or research firms serve unions; most have a strong pro-business bias that accompanies their reliance on large corporate accounts. As a result, most unions stand at a distinct disadvantage when it comes to refuting company claims of hardship. This weakens both the leadership and membership, and makes it difficult for unions to present their case to the press and the public. At Eastern Air Lines, two unions used very different approaches to analyze the company's financial condition. The pilots hired a prestigious corporate accounting firm. A partner in this firm flew down to Eastern's Miami headquarters for a half day presentation.In a subsequent 30-minute oral report to the union leadership he "confirmed" that Eastern was in bad shape, thereby justifying concession demands. Nothing was put in writing for the membership and the fee was $5000. IAM District 100 took a different approach. The leadership decided first to educate themselves about Eastern's finances in order to independently assess the company's condition. They realized that this required a solid understanding of basic accounting principles. For guidance, they turned to experts not beholden to company clients. Finally the IAM leadership educated the total membership about what they had learned.
Induction of the Early Growth Response Gene 1 Promoter by TCR Agonists and Partial Agonists: Ligand Potency Is Related to Sustained Phosphorylation of Extracellular Signal-Related Kinase Substrates (2003)

Responses to partial agonist TCR signals include positive selection of thymocytes, survival of naive T cells, and homeostatic proliferation. As part of an effort to understand the molecular basis of these processes, we have determined how agonist and partial agonist ligands act differently to induce a change in gene expression. We have found that the early growth response gene 1 (Egr1) promoter is activated by agonist and partial agonist ligands, but the partial agonist induces 10-fold lower promoter activity. Both agonist and partial agonist ligands require all six serum response elements in the Egr1 promoter to reach maximum induction. Although slightly fewer cells respond to the partial agonist, all of the responding cells have reduced activity compared with the cells responding to agonist. The factors binding to the serum response elements of the Egr1 promoter form a ternary complex (TC) consisting of serum response factor and either Elk-1 or serum response factor accessory protein-1a. Formation of a stable TC and inducible promoter activity are both dependent on extracellular signal-related kinase activation. Examination of TC formation over time reveals that this complex is induced well by partial agonist ligands, but it is not sustained, whereas agonist stimulation induces longer lived TCs. Therefore, the data suggest that both agonist and partial agonist ligands can induce formation of multiple TC on the Egr1 promoter, but the ability of the agonist ligand to maintain these complexes for an extended time results in the increased potency of the agonist.
Adaptive interface for text input on large-scale interactive surfaces (2008)

In this paper we present a novel approach to text input on large interactive surfaces using a combination of strategies to resolve the inherent difficulties with text input on such a device. Instead of using a conventional full size QWERTY based layout, the idea is to use a very limited set of buttons that, by using word prediction and hints, would only require minimal finger movement. The input mechanism is somewhat related to input methods employed when using keyboards with a limited size and amount of keys, commonly found in phones and other 10 digit keyboards. Given that the main motivation to this approach was not the limited size but rather to overcome the difficult task of locating keys with fingers on a flat and featureless surface, making touch-typing very difficult and requiring frequent visual monitoring of the finger position, we opted to enhance the interaction with easily made gestures, a layout that adapts to the hand anatomy of the user, and easy control over the text prediction.
A role for histone deacetylase activity in HDAC1-mediated transcriptional repression (1998)

Treatment of mammalian cells with small molecule histone deacetylase (HDAC) inhibitors induces changes in the transcription of specific genes. These changes correlate directly with an increase in the acetylation levels of all four core histones in vivo. Antibodies directed against endogenous HDAC1, HDAC2, or HDAC3 immunoprecipitate histone deacetylase activity that is inhibited in vitro by the small molecule trapoxin (TPX), and all three HDACs are retained by a TPX-affinity matrix. HDAC1 and HDAC2 are associated in HeLa cells in a complex that is predominantly separate from an HDAC3 immune complex. Both Jurkat HDAC1 and HeLa HDAC1/2 immune complexes deacetylate all four core histones and recombinant HDAC1 deacetylates free and nucleosomal histones in vitro. Purified recombinant HDAC1 deacetylates core histones in the absence of protein cofactors. Site-directed mutagenesis was used to identify residues required for the enzymatic and structural integrity of HDAC1. Mutation of any one of four conserved residues causes deleterious effects on deacetylase activity and a reduced ability to bind a TPX-affinity matrix. A subset of these mutations also cause a decreased interaction with the HDAC1-associated proteins RbAp48 and mSin3A. Disruption of histone deacetylase activity either by TPX or by direct mutation of a histidine presumed to be in the active site abrogates HDAC1-mediated transcriptional repression of a targeted reporter gene in vivo.
Expression Profile of Active Genes in Granulocytes (1998)

A number of genes active in granulocytes have been intensively studied as to the function of their products and their expression controls. However, the intensities and relative order of these gene activities have not been studied. This report describes an expression profile of 748 different species of active genes in human peripheral granulocytes obtained by analyzing a 3'-directed cDNA library that faithfully represents the mRNA population in the source cells. A significant fraction (20.3% of the total) of the expressed genes in granulocytes consisted of nuclear proteins such as DNA binding proteins, of secretory proteins such as cytokines, and of membrane proteins such as major histocompatibility complex (MHC) proteins and receptors. By comparing this expression profile with 11 profiles similarly obtained with unrelated human cells/tissues, we discovered 10 novel genes that are likely to act specifically in granulocytes. Comparison of this expression profile with that obtained with granulocytoids widely used as a granulocyte model by inducing a cultured promyelocytic leukemia cell line HL60 showed similarities and dissimilarities of gene expressions.
Echocardiography in the assessment of complications of myocardial infarction. (1991)

The value of echocardiography as a tool for evaluating the prognosis of patients after myocardial infarction lies in its ability to define the region and extent of ischemic damage. Additionally, echocardiography is useful in assessing and predicting postinfarction complications. Wall motion abnormalities, pericardial effusion, left ventricular thrombi, and left ventricular aneurysms and pseudoaneurysms can be detected using echocardiography. The severity of mitral regurgitation and the location of interventricular septal rupture can also be assessed using echocardiography. This diagnostic tool can provide vital information regarding the appropriate clinical management of patients after myocardial infarction.
Insulin Exocytosis and Glucose-mediated Increase in Cytoplasmic Free Ca2+ Concentration in the Pancreatic β-Cell Are Independent of Cyclic ADP-ribose (1996)

Stimulation of pancreatic beta-cells by glucose gives rise to an increase in the cytoplasmic free calcium concentration ([Ca2+]i) and exocytosis of insulin. Cyclic adenosine 5'-diphosphate ribose (cADPR), a metabolite of beta-NAD+, has been reported to increase [Ca2+]i in pancreatic beta-cells by releasing Ca2+ from inositol 1,4,5-trisphosphate-insensitive intracellular stores. In the present study, we have examined the role of cADPR in glucose-mediated increases in [Ca2+]i and insulin exocytosis. Dispersed ob/ob mouse beta-cell aggregates were either pressure microinjected with fura-2 salt or loaded with fura-2 acetoxymethyl ester, and [Ca2+]i was monitored by microfluorimetry. Microinjection of beta-NAD+ into fura-2-loaded beta-cells did not increase [Ca2+]i nor did it alter the cells' subsequent [Ca2+]i response to glucose. Cells microinjected with the cADPR antagonist 8NH2-cADPR increased [Ca2+]i in response to glucose equally well as those injected with cADPR. Finally, the ability of cADPR to promote exocytosis of insulin in electropermeabilized beta-cells was investigated. cADPR on its own did not increase insulin secretion nor did it potentiate Ca2+-induced insulin secretion. We conclude that cADPR neither plays a significant role in glucose-mediated increases in [Ca2+]i nor interacts directly with the molecular mechanisms regulating exocytosis of insulin in normal pancreatic beta-cells.
Production of humanized monoclonal antibodies for in vivo imaging and therapy (1995)

Conference Article| November 01 1995 Production of humanized monoclonal antibodies for in vivo imaging and therapy W. J. Harris W. J. Harris 1Department of Molecular and Cell Biology, University of Aberdeen, Marischal College, Aberdeen AB9 IAS, Scotland, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1995) 23 (4): 1035–1038. https://doi.org/10.1042/bst0231035 Article history Received: June 14 1995 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation W. J. Harris; Production of humanized monoclonal antibodies for in vivo imaging and therapy. Biochem Soc Trans 1 November 1995; 23 (4): 1035–1038. doi: https://doi.org/10.1042/bst0231035 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1995 Biochemical Society1995 Article PDF first page preview Close Modal You do not currently have access to this content.
TELOMERES AND THEIR CONTROL (2000)

Telomeres are DNA and protein structures that form complexes protecting the ends of chromosomes. Understanding of the mechanisms maintaining telomeres and insights into their function have advanced considerably in recent years. This review summarizes the currently known components of the telomere/telomerase functional complex, and focuses on how they act in the control of processes occurring at telomeres. These include processes acting on the telomeric DNA and on telomeric proteins. Key among them are DNA replication and elongation of one telomeric DNA strand by telomerase. In some situations, homologous recombination of telomeric and subtelomeric DNA is induced. All these processes act to replenish or restore telomeres. Conversely, degradative processes that shorten telomeric DNA, and nonhomologous end-joining of telomeric DNA, can lead to loss of telomere function and genomic instability. Hence they too must normally be tightly controlled.
Risk of Primary Infection and Reinfection With Respiratory Syncytial Virus (1986)

Respiratory syncytial virus is the most important cause of serious lower respiratory tract infection in children. For children followed up from birth in the Houston Family Study, the infection rate was 68.8/100 children less than 12 months of age and 82.6/100 during the second year of life. Virtually all children had been infected at least once by 24 months of age, and about one half had experienced two infections. Although lower respiratory tract disease (LRD) was common (22.4/100 during year 1 and 13.0/100 during year 2), most children had only one LRD illness. The risk of reinfection was inversely related to the level of neutralizing antibodies in the serum. Reinfection illnesses were generally mild, and risk of reinfection decreased to only 33.3/100 during year 4. Studies of children with LRD and surveys of hospitalizations provide the basis for an estimate of the number of children hospitalized each year during the respiratory syncytial virus epidemics. Almost 100,000 children in the United States experience an illness of sufficient severity to require hospitalization.
Some Attenuated Variants of Vesicular Stomatitis Virus Show Enhanced Oncolytic Activity against Human Glioblastoma Cells relative to Normal Brain Cells (2009)

Vesicular stomatitis virus (VSV) has been shown in laboratory studies to be effective against a variety of tumors, including malignant brain tumors. However, attenuation of VSV may be necessary to balance the potential toxicity toward normal cells, particularly when targeting brain tumors. Here we compared 10 recombinant VSV variants resulting from different attenuation strategies. Attenuations included gene shifting (VSV-p1-GFP/RFP), M protein mutation (VSV-M51), G protein cytoplasmic tail truncations (VSV-CT1/CT9), G protein deletions (VSV-dG-GFP/RFP), and combinations thereof (VSV-CT9-M51). Using in vitro viability and replication assays, the VSV variants were grouped into three categories, based on their antitumor activity and non-tumor-cell attenuation. In the first group, wild-type-based VSV-G/GFP, tumor-adapted VSV-rp30, and VSV-CT9 showed a strong antitumor profile but also retained some toxicity toward noncancer control cells. The second group, VSV-CT1, VSV-dG-GFP, and VSV-dG-RFP, had significantly diminished toxicity toward normal cells but showed little oncolytic action. The third group displayed a desired combination of diminished general toxicity and effective antitumor action; this group included VSV-M51, VSV-CT9-M51, VSV-p1-GFP, and VSV-p1-RFP. A member of the last group, VSV-p1-GFP, was then compared in vivo against wild-type-based VSV-G/GFP. Intranasal inoculation of young, postnatal day 16 mice with VSV-p1-GFP showed no adverse neurological effects, whereas VSV-G/GFP was associated with high lethality (80%). Using an intracranial tumor xenograft model, we further demonstrated that attenuated VSV-p1-GFP targets and kills human U87 glioblastoma cells after systemic application. We concluded that some, but not all, attenuated VSV mutants display a favorable oncolytic profile and merit further investigation.
Molecular characterization of human Ig heavy chain DIR genes. (1994)

Antibody VDJ recombination is ensured by evolutionarily conserved recombination signals (RS). The 12/23 rule postulates that only gene segments with asymmetrically spaced RS recombine with one another. Two unusually long D genes (170 bp) with irregular RS (DIR) have been reported in humans and have been postulated to participate actively in VDJ recombination, thus frequently contributing to the Ab heavy chain third hypervariable region (CDR3). However, the limited sequence information retained in the CDR3 along with significant sequence diversity has precluded an accurate assessment of the actual role and genomic diversity of DIR genes. Furthermore, DIR genes pose an interesting puzzle in terms of their precise mechanism of recombination because they possess multiple and imperfect RS, often located up to 30 bp away from the recombining fragment within the DIR coding region. Here we present conclusive evidence for the existence of additional human germ-line DIR genes and preliminary evidence that suggests the absence of DIR-like sequences in nonprimate animals. We also show that DIR genes are under the transcriptional control of VH-independent promoters and have the potential to encode a D mu protein of 105 amino acids. Finally, DIR genes seem at least in early fetal life to recombine preferentially through the conventional 3' RS.
Procyclin gene expression and loss of the variant surface glycoprotein during differentiation of Trypanosoma brucei. (1989)

In the mammalian host, the unicellular flagellate Trypanosoma brucei is covered by a dense surface coat that consists of a single species of macromolecule, the membrane form of the variant surface glycoprotein (mfVSG). After uptake by the insect vector, the tsetse fly, bloodstream-form trypanosomes differentiate to procyclic forms in the fly midgut. Differentiation is characterized by the loss of the mfVSG coat and the acquisition of a new surface glycoprotein, procyclin. In this study, the change in surface glycoprotein composition during differentiation was investigated in vitro. After triggering differentiation, a rapid increase in procyclin-specific mRNA was observed. In contrast, there was a lag of several hours before procyclin could be detected. Procyclin was incorporated and uniformly distributed in the surface coat. The VSG coat was subsequently shed. For a single cell, it took 12-16 h to express a maximum level of procyclin at the surface while the loss of the VSG coat required approximately 4 h. The data are discussed in terms of the possible molecular arrangement of mfVSG and procyclin at the cell surface. Molecular modeling data suggest that a (Asp-Pro)2 (Glu-Pro)22-29 repeat in procyclin assumes a cylindrical shape 14-18 nm in length and 0.9 nm in diameter. This extended shape would enable procyclin to interdigitate between the mfVSG molecules during differentiation, exposing epitopes beyond the 12-15-nm-thick VSG coat.