gebhart/patrepeval huggingface dataset:
Vaccinia virus morphogenesis is interrupted when expression of the gene encoding an 11-kilodalton phosphorylated protein is prevented by the Escherichia coli lac repressor (1991)

A conditional lethal vaccinia virus mutant, which constitutively expresses the Escherichia coli lac repressor and has the lac operator controlling the F18R gene (the 18th open reading frame of the HindIII F fragment of the vaccinia virus strain WR genome) encoding an 11-kDa protein, was previously shown to be dependent on the inducer isopropyl-beta-D-thiogalactoside (IPTG) for replication (Y. Zhang and B. Moss, Proc. Natl. Acad. Sci. USA 88:1511-1515, 1991). Further studies indicated that the yield of infectious virus could be regulated by titration with IPTG and that virus production was arrested by IPTG removal at appropriate times. Under nonpermissive conditions, an 11-kDa protein reactive with antiserum raised to a previously described DNA-binding phosphoprotein (S. Y. Kao and W. R. Bauer, Virology 159:399-407, 1987) was not synthesized, indicating that the latter is the product of the F18R gene. In the absence of IPTG, replication of viral DNA and the subsequent resolution of concatemeric DNA molecules appeared normal. Omission of IPTG did not alter the kinetics of early and late viral protein synthesis, although the absence of the 11-kDa polypeptide was noted by labeling infected cells with [35S]methionine or [32P]phosphate. Pulse-chase experiments revealed that proteolytic processing of the major viral structural proteins, P4a and P4b, was inhibited under nonpermissive conditions, suggesting a block in virus maturation. Without addition of IPTG, the failure of virus particle formation was indicated by sucrose gradient centrifugation of infected cell lysates and by the absence of vaccinia virus-mediated pH-dependent cell fusion. Electron microscopic examination of infected cells revealed that immature virus particles, with aberrant internal structures, accumulated when synthesis of the 11-kDa DNA-binding protein was prevented.
Fluorescence correlation analysis of probe diffusion simplifies quantitative pathogen detection by PCR (1996)

A sensitive, labor-saving, and easily automatable nonradioactive procedure named APEX-FCS (amplified probe extension detected by fluorescence correlation spectroscopy) has been established to detect specific in vitro amplification of pathogen genomic sequences. As an example, Mycobacterium tuberculosis genomic DNA was subjected to PCR amplification with the Stoffel fragment of Thermus aquaticus DNA polymerase in the presence of nanomolar concentrations of a rhodamine-labeled probe (third primer), binding to the target in between the micromolar amplification primers. The probe becomes extended only when specific amplification occurs. Its low concentration avoids false-positives due to unspecific hybridization under PCR conditions. With increasing portion of extended probe molecules, the probe's average translational diffusion properties gradually change over the course of the reaction, reflecting amplification kinetics. Following PCR, this change from a stage of high to a stage of low mobility can directly be monitored during a 30-s measurement using a fluorescence correlation spectroscopy device. Quantitation down to 10 target molecules in a background of 2.5 micrograms unspecific DNA without post-PCR probe manipulations could be achieved with different primer/ probe combinations. The assay holds the promise to concurrently perform amplification, probe hybridization, and specific detection without opening the reaction chamber, if sealable foils are used.
The Irish body snatchers. John Fleetwood. Dublin: Tomar, 1989. 141 pp, IR£4.95. (1991)

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Creating Random Mutagenesis Libraries by Megaprimer PCR of Whole Plasmid (MEGAWHOP) (2003)

The conventional method for cloning a DNA fragment is to insert it into a vector and ligate it (1). Although this method is commonly used, it is labor intensive because the ratio and concentrations of the DNA insert and the vector must be optimized. Even then, the resulting library is often plagued with unwanted plasmids that have no inserts or multiple inserts. These species have to be eradicated to avoid tedious screening, especially when producing random mutagenesis libraries.
Relapse rates after short-course (6-month) treatment of tuberculosis in HIV-infected and uninfected persons (1999)

These results support current recommendations to treat tuberculosis in HIV-infected patients with short-course (6-month) therapy.
Construction of a Double Recombinant Adenovirus Vector Expressing a Heterodimeric Cytokine: In Vitro and In Vivo Production of Biologically Active Interleukin-12 (1996)

Interleukin-12 (IL-12) is a heterodimeric cytokine that plays an important role in the development of cellular immunity. Clinical applications for this lymphokine include resolution of infectious disease, cancer immunotherapy, and boosting cellular immunity in AIDS patients. When using IL-12 and other cytokines therapeutically, an approach designed to obtain localized cytokine expression would be beneficial, because this could reduce the problem of systemic toxicity. As a means of developing a suitable delivery vehicle for IL-12, we have produced double-recombinant adenovirus vectors containing the p35 subunit cDNA of murine IL-12 in early region 1 of adenovirus type 5 and the cDNA for p40 in early region 3 (AdmIL-12). Cell lines infected with AdmIL-12 produced up to 42,000 units of IL-12/10(6) cells per 24 hr. Biological activity of the virally expressed product was demonstrated in vitro through its ability to induce proliferation of phytohemagglutinin (PHA)-stimulated lymphoblasts and to stimulate natural killer (NK) activity in naive splenocytes. Mice injected intraperitoneally with these vectors displayed serum IL-12 levels that increased proportionately with the amount of virus administered. IL-12 production in vivo caused a dose-dependent increase in splenic and lung NK cell activity. This work represents the first demonstration of a double-recombinant adenovirus vector expressing a functional heterodimeric protein. The results of these studies support the use of AdmIL-12 as an efficient delivery vehicle for IL-12, and direct studies of its ability to modulate cellular immunity in vivo are currently underway.
Nucleic Acid Aptamers Against Biotoxins: A New Paradigm Toward the Treatment and Diagnostic Approach (2012)

Nucleic acid aptamers are short single-stranded DNA or RNA oligonucleotides that can bind to their targets with very high affinity and specificity, and are generally selected by a process referred to as systematic evolution of ligands by exponential enrichment. Conventional antibody-based therapeutic and diagnostic approach currently employed against biotoxins pose major limitations such as the requirement of a live animal for the in vivo enrichment of the antibody species, decreased stability, high production cost, and side effects. Aptamer technology is a viable alternative that can be used to combat these problems. Fully sequestered in vitro, aptamers eliminate the need for a living host. Furthermore, one of the key advantages of using aptamers instead of antibodies is that they can be selected against very weakly immunogenic and cytotoxic substances. In this review, we focus on nucleic acid aptamers developed against various biotoxins of plant, microorganism, or animal origin and show how these can be used in diagnostics (e.g., biosensors) and therapy.
High Thrombopoietin Production by Hematopoietic Cells Induces a Fatal Myeloproliferative Syndrome in Mice (1997)

To evaluate the effects of long-term, high-dose exposure to thrombopoietin (TPO), lethally irradiated mice were grafted with bone marrow cells infected with a retrovirus carrying the murine TPO cDNA. Mice were studied for 10 months after transplantation. In plasma, TPO levels were highly elevated (10(4) U/mL) throughout the course of the study. All mice developed a lethal myeloproliferative disorder evolving in two successive phases. During the first phase (7-9 weeks posttransplant), platelet and white blood cell (WBC) counts rose four- and ten-fold, respectively, whereas hematocrits decreased slightly to 29% +/- 3%. The WBC were mainly mature granulocytes, but myeloid precursor cells were invariably observed as well as giant platelets with an irregular granule distribution. The striking features were a massive hyperplasia of megakaryocytes and granulocytes in the spleen and bone marrow and a hypoplasia of erythroblasts in bone marrow. Total numbers of megakaryocyte colony-forming cell, burst-forming unit-erythroid, and granulocyte macrophage colony-forming cells were increased but colony-forming unit-erythroid numbers decreased. From 10 weeks posttransplant and thereafter, WBC, platelets, and red blood cell numbers declined dramatically. The absolute numbers of progenitor cells were very low in the spleen and bone marrow, but sharply increased in the blood and peritoneal cavity. Extramedullary hematopoiesis was observed in several organs. Histologic sections of the spleen and bones revealed severe fibrosis and osteosclerosis. The mean survival time was 7 months posttransplant and mice died with severe pancytopenia. Notably, two mice died between 3 and 4 months posttransplant with a leukemic transformation. This disorder was transplantable into secondary recipients who developed an attenuated form of the disease similar to the one previously described (Yan et al, Blood 86:4025, 1995). Taken together, our data show that high and persistent TPO production by transduced hematopoietic cells in mice results in a fatal myeloproliferative disorder that has a number of features in common with human idiopathic myelofibrosis.
Efficacy of Esomeprazole (20 mg Once Daily) for Reducing the Risk of Gastroduodenal Ulcers Associated With Continuous Use of Low-Dose Aspirin (2008)

Esomeprazole 20 mg once daily reduces the risk of developing gastric and/or duodenal ulcers and symptoms associated with the continuous use of low-dose aspirin in patients aged > or =60 yr without preexisting gastroduodenal ulcers.
Epigenetic control of the E‐cadherin gene (CDH1) by CpG methylation in colectomy samples of patients with ulcerative colitis (2002)

E-cadherin belongs to the cadherin family of calcium-dependent cell-adhesion molecules. The cadherins play an essential role in biological processes such as ordering of cell sorting, migration, and differentiation, and their malfunctioning is connected with neoplasia. Neoplastic progression in patients with chronic ulcerative colitis is characterized by the development of epithelial dysplasia. Transcriptional silencing of tumor-suppressor genes by promoter methylation has been observed in different types of human cancers and dysplasia. To explore the mode of E-cadherin regulation, 156 biopsy samples from 26 patients with long-standing ulcerative colitis were screened. To detect the methylation status of our samples, a methylation-specific PCR was applied. Methylation of the E-cadherin (CDH1) promoter was detected in 93% of the patients with dysplastic biopsy samples, in contrast to only 6% of the patients without dysplasia (P < 0.001). We also examined the level of synthesis of E-cadherin protein by immunohistochemical staining in different paraffin-embedded samples of dysplastic and non-dysplastic origin in a subset of our patients. Samples with dysplasia displayed reduced levels, whereas samples without dysplasia revealed normal E-cadherin protein synthesis. These results show that the E-cadherin promoter is subjected to epigenetic control in colorectal ulceration. Obviously, this event may play an important role in the progression from chronic inflammation to colorectal cancer. For this reason, methylation of the CDH1 promoter is an attractive new biomarker for detecting ulcerative colitis patients with a high risk for developing colorectal cancers.
C-myc, N-myc, N-ras, and c-erb-B: lack of amplification or rearrangement in human medullary thyroid carcinoma and a derivative cell line. (1990)

We investigated the copy number and possible rearrangement of the four protooncogenes, c-myc, N-myc, N-ras, and c-erb-B, in DNA from seven untreated primary cancers or metastases of medullary thyroid carcinoma and an established human medullary thyroid carcinoma cell line, TT, using the Southern blotting technique. The purpose of this study was two-fold: 1) to examine whether protooncogene perturbations in medullary thyroid carcinoma could be considered as a prognostic marker; and 2) to determine whether the protooncogenes could have a possible role in medullary thyroid tumorigenesis. Neither amplification nor rearrangement of the protooncogenes was detectable in the DNA from any tumor samples or in the cell line. Our results suggest that DNA-evident amplification and rearrangement of the c-myc, N-myc, N-ras, and c-erb-B oncogenes may not be mechanisms through which these oncogenes become activated in this malignancy.
Faithful reconstruction of digital holograms captured by FINCH using a Hamming window function in the Fresnel propagation (2013)

Recent advances in Fresnel incoherent correlation holography (FINCH) increase the signal-to-noise ratio in hologram recording by interference of images from two diffractive lenses with focal lengths close to the image plane. Holograms requiring short reconstruction distances are created that reconstruct poorly with existing Fresnel propagation methods. Here we show a dramatic improvement in reconstructed fluorescent images when a 2D Hamming window function substituted for the disk window typically used to bound the impulse response in the Fresnel propagation. Greatly improved image contrast and quality are shown for simulated and experimentally determined FINCH holograms using a 2D Hamming window without significant loss in lateral or axial resolution.
IL-12 synergizes with IL-18 or IL-1β for IFN-γ production from human T cells (2000)

IL-18 is a proinflammatory cytokine that plays an important role in NK cell activation and T(h)1 response. IL-18 has a structural homology to IL-1, particularly IL-1beta. IL-18R, composed of IL-1R-related protein (IL-18Ralpha) and IL-1R accessory protein-like (IL-18Rbeta), belongs to the IL-1R family. Furthermore, IL-18R at least partly shares the signal transducing system with IL-1R. Thus, the IL-18-IL-18R system has a striking similarity to the IL-1-IL-1R system. For this reason, we regarded it important to investigate whether, like IL-18, IL-1beta synergizes with IL-12 in inducing IFN-gamma production from human T cells and plays an important role in the T(h)1 response. Here we show that IL-12 and IL-1beta synergistically induce T cells to proliferate and produce IFN-gamma without their TCR engagement. IL-12 stimulation induced an increase in the proportion of T cells positive for IL-18R. Then, IL-12-stimulated T cells responded to IL-18 or IL-1beta by their proliferation and IFN-gamma production, although levels of IL-1beta-induced responses were lower. CD4(+)CD45RA(+) T cells, although they constitutively expressed IL-18Rbeta mRNA, did not express IL-18Ralpha mRNA. Phytohemagglutinin (PHA) stimulation alone induced IL-18Ralpha mRNA without affecting the expression of IL-18Rbeta mRNA. T(h)1-inducing conditions (PHA, IL-12 and anti-IL-4) further increased this expression. We also show that T(h)1 cells but not T(h)2 cells have increased expression of IL-18R and IL-1R, and produce IFN-gamma in response to IL-18 and/or IL-1beta.
Postmodification Approach to Charge-Tagged 1,2,4-Triazole-Derived NHC Palladium(II) Complexes and Their Applications (2017)

Charge-tagged bis(1,2,4-triazolin-5-ylidene)palladium(II) complexes have been successfully synthesized via a postmodification strategy. Reacting PdBr2 with bromo-functionalized 1,2,4-triazolium salts A·HBr and B·HBr in the presence of silver oxide afforded the bis(carbene)palladium(II) complexes trans-[PdBr2(A)2] (1a) and trans-[PdBr2(B)2] (1b), which contain tethered bromoalkyl chains. Subsequent postcoordinative nucleophilic substitution converted the bromo into ammonium groups, producing the water-soluble complexes trans-[PdBr2(C)2]Br2 (2a) and trans-[PdBr2(D)2]Br2 (2b), while attempts to prepare ammonium-functionalized triazolium salts for direct metalation were futile. All four complexes were fully characterized by means of multinuclear NMR spectroscopy, ESI mass spectrometry, elemental analysis, and X-ray diffraction analysis. The presence of trans-anti and trans-syn rotameric complexes in solution was elucidated by 1H and 13C NMR spectroscopy and theoretical calculations. Additionally, the two charge-tagged complexes, 2a,b, were found to be highly active precatalysts for the Suzuki–Miyaura and Mizoroki-Heck reactions in iPrOH/H2O and molten TBAB as an ionic liquid.
Inflammatory Cytokines in Experimental and Human Stroke (2012)

Inflammation is a hallmark of stroke pathology. The cytokines, tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, modulate tissue injury in experimental stroke and are therefore potential targets in future stroke therapy. The effect of these cytokines on infarct evolution depends on their availability in the ischemic penumbra in the early phase after stroke onset, corresponding to the therapeutic window (<4.5 hours), which is similar in human and experimental stroke. This review summarizes a large body of literature on the spatiotemporal and cellular production of TNF, IL-1, and IL-6, focusing on the early phase in experimental and human stroke. We also review studies of cytokines in blood and cerebrospinal fluid in stroke. Tumor necrosis factor and IL-1 are upregulated early in peri-infarct microglia. Newer literature suggests that IL-6 is produced by microglia, in addition to neurons. Tumor necrosis factor- and IL-1-producing macrophages infiltrate the infarct and peri-infarct with a delay. This information is discussed in the context of suggestions that neuronal sensitivity to ischemia may be modulated by cytokines. The fact that TNF and IL-1, and suppossedly also IL-6, are produced by microglia within the therapeutic window place these cells centrally in potential future stroke therapy.
The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells (2006)

CCR7 was described initially as a potent leukocyte chemotactic receptor that was later shown to be responsible of directing the migration of dendritic cells (DCs) to the lymph nodes where these cells play an important role in the initiation of the immune response. Recently, a variety of reports have indicated that, apart from chemotaxis, CCR7 controls the cytoarchitecture, the rate of endocytosis, the survival, the migratory speed, and the maturation of the DCs. Some of these functions of CCR7 and additional ones also have been described in other cell types. Herein we discuss how this receptor may contribute to modulate the immune response by regulating different functions in DCs. Finally, we also suggest a possible mechanism whereby CCR7 may control its multiple tasks in these cells.
Natural protein proteinase inhibitors and their interaction with proteinases (1992)

The substrate-like 'canonical' inhibition by the 'small' serine proteinase inhibitors and the product-like inhibition by the carboxypeptidase inhibitor have provided the only atomic models of protein inhibitor--proteinase interactions for about 15 years. The recently published structures of cystatin/stefin--papain complexes and of hirudin--thrombin complexes reveal novel non-substrate-like interactions. In addition, the structure of pro-carboxypeptidase shows a model of inactivation which bears resemblance to proteinase/protein inhibitor systems. Considerable progress in understanding the transition between native and cleaved states of the serpins has also been made by several recent structural studies.
Control Gate Length, Spacing and Stacked Layer Number Design for 3D-Stackable NAND Flash Memory (2012)

Scaling and device design for 3D-stackable NAND (3D NAND) flash memory are investigated. Control gate length (Lg) and spacing (Lspace) are paid attention since they can be separately varied in 3D NAND and significantly affect the cell area of the 3D NAND as well as the electrical characteristics. The requirements for the Lg and Lspace are derived from the 3D device simulation and the cell size to compete with the planar NAND. The simulations reveal that Lg=Lspace=20nm (40nm layer pitch) is achievable for BiCS type 3D NAND with the 90nm diameter hole. Programming voltage can be also reduced from 20V to 17V. Lg and Lspace should be the same to cope with the tradeoff between memory window and disturbance. If the number of stacked layers is 18 with the layer pitch of 40nm, the effective cell size of the 3D NAND corresponds to that of 15nm planar NAND technology.
Formation of droplets using branch channels in a microfluidic circuit (2003)

This paper presents a new method for preparing micro droplets inside the liquid layer at a T-junction in a microchannel network. The relations between droplet size, flow speed, and channel size are studied. The droplet size is easily varied by changing the flow conditions in the microchannels. The size distribution of the resulting droplets is very narrow.
Contribution of the glutamine 19 side chain to transition-state stabilization in the oxyanion hole of papain (1991)

The existence of an oxyanion hole in cysteine proteases able to stabilize a transition-state complex in a manner analogous to that found with serine proteases has been the object of controversy for many years. In papain, the side chain of Gln19 forms one of the hydrogen-bond donors in the putative oxyanion hole, and its contribution to transition-state stabilization has been evaluated by site-directed mutagenesis. Mutation of Gln19 to Ala caused a decrease in kcat/KM for hydrolysis of CBZ-Phe-Arg-MCA, which is 7700 M-1 s-1 in the mutant enzyme as compared to 464,000 M-1 s-1 in wild-type papain. With a Gln19Ser variant, the activity is even lower, with a kcat/KM value of 760 M-1 s-1. The 60- and 600-fold decreases in kcat/KM correspond to changes in free energy of catalysis of 2.4 and 3.8 kcal/mol for Gln19Ala and Gln19Ser, respectively. In both cases, the decrease in activity is in large part attributable to a decrease in kcat, while KM values are only slightly affected. These results indicate that the oxyanion hole is operational in the papain-catalyzed hydrolysis of CBZ-Phe-Arg-MCA and constitute the first direct evidence of a mechanistic requirement for oxyanion stabilization in the transition state of reactions catalyzed by cysteine proteases. The equilibrium constants Ki for inhibition of the papain mutants by the aldehyde Ac-Phe-Gly-CHO have also been determined. Contrary to the results with the substrate, mutation at position 19 of papain has a very small effect on binding of the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)