gebhart/patrepeval huggingface dataset:
MERS-CoV and SARS-CoV-2 replication can be inhibited by targeting the interaction between the viral spike protein and the nucleocapsid protein (2021)

<b>Background:</b> The molecular interactions between viral proteins form the basis of virus production and can be used to develop strategies against virus infection. The interactions of the envelope proteins and the viral RNA-binding nucleocapsid (N) protein are essential for the assembly of coronaviruses including the Middle East respiratory syndrome coronavirus (MERS-CoV). <b>Methods:</b> Using co-immunoprecipitation, immunostaining, and proteomics analysis, we identified a protein interacting with the spike (S) protein in the cells infected with MERS-CoV or SARS-CoV-2. To confirm the interaction, synthetic peptides corresponding to the C-terminal domain of the S protein (Spike CD) were produced and their effect on the interaction was investigated <i>in vitro</i>. <i>In vivo</i> effect of the Spike CD peptides after cell penetration was further investigated using viral plaque formation assay. Phylogeographic analyses were conducted to deduce homology of Spike CDs and N proteins. <b>Results:</b> We identified a direct interaction between the S protein and the N protein of MERS-CoV that takes place during virus assembly in infected cells. Spike CD peptides of MERS-CoV inhibited the interaction between the S and N proteins <i>in vitro.</i> Furthermore, cell penetration by the synthetic Spike CD peptides inhibited viral plaque formation in MERS-CoV-infected cells. Phylogeographic analyses of Spike CDs and N proteins showed high homology among betacoronavirus lineage C strains. To determine if Spike CD peptides can inhibit the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we used the same strategy and found that the SARS-CoV-2 Spike CD peptide inhibited virus replication in SARS-CoV-2-infected cells. <b>Conclusions:</b> We suggest that the interaction between the S protein and the N protein can be targeted to design new therapeutics against emerging coronaviruses, including SARS-CoV-2.
C <sub>4</sub> -dicarboxylate transport mutants of <i>Rhizobium trifolii</i> form ineffective nodules on <i>Trifolium repens</i> (1981)

Mutants of Rhizobium trifolii strain 7012 defective in C(4)-dicarboxylate transport were isolated by using a selective procedure based on pH indicator media. The mutant strains CR7098 and CR7099 failed to grow on or transport succinate, fumarate, or malate, but grew at wild-type rates on several other carbon sources. The C(4)-dicarboxylate transport system was inducible in strain 7012, but was expressed constitutively in four out of five succinate-positive revertants of strain CR7098. In the fifth CR7098 revertant (strain CR8008) the system was inducible. However, in contrast to strain 7012, strain CR8008 failed to use the C(4)-dicarboxylates in the presence of a second carbon source. Revertants of strain CR7099 were similar to strain 7012. Both strains CR7098 and CR7099 nodulated white and red clover at a rate similar to that of strain 7012, but nodules formed by the mutant strains were white and ineffective. Microscopic examination showed that the pattern of development of white clover nodules formed by strain CR7098 was similar to that observed with nodules formed by strain 7012, except that large amounts of starch accumulated in bacteroid-filled cells and senescence occurred earlier. Revertant strains were effective, except for strain CR8008, which formed ineffective nodules. The results show that a supply of C(4)-dicarboxylates to bacteroids is essential for nitrogen fixation in clover nodules. However, rhizobia within plant cells must also utilize other carbon sources to support growth and division.
Functional Hyperbranched Polymers: Toward Targeted <i>in Vivo</i> <sup>19</sup>F Magnetic Resonance Imaging Using Designed Macromolecules (2010)

We have demonstrated the design and synthesis of hyperbranched molecules that can be successfully imaged in vivo using (19)F MRI in under 10 min. These polymers are cytocompatible following chain extension with PEGMA. In addition, functionalization of these macromolecules can be achieved in a facile manner and with accessible and correct ligand presentation. Such hyperbranched polymers hold promise as new generation tracking and targeting MRI contrast agents.
VASCULAR STRUCTURE SEGMENTATION AND BIFURCATION DETECTION (2007)

Delineation and reconstruction of vascular structures in medical images are critical for the diagnosis of various vascular diseases and related surgical procedures. In this paper, we present a novel method for vascular structure segmentation with fully automatic detection of bifurcation points. First, we perform a preselection of tubular objects and trace the vessels based on the eigenanalysis of the Hessian matrix. This provides us the estimated direction of vessels as well as the cross-sectional planes orthogonal to the vessels. Then, we apply AdaBoost learning method with specially designed filters on cross-sectional planes to automatically detect the bifurcation points of the vessels. Our method has over 97% success rate for detecting bifurcation points. We present very promising results of our method applied to the reconstruction of pulmonary vessels from clinical chest CT. Our method allows for fully automatic detection of bifurcation points as well as segmentation of vessels
Performance of skeletal muscle ventricles: effects of ventricular chamber size. (1990)

Skeletal muscle ventricles were constructed in 12 dogs. In one group of dogs (n = 7) the skeletal muscle ventricles were constructed around a 17 ml Teflon mandrel, and in the other group (n = 5) a 45 ml mandrel was used. Use of the larger mandrel resulted in an increase in compliance and greater stroke work over the physiologic range of preloads and afterloads. With the larger mandrel, stroke work consistently exceeded normal canine stroke work at physiologic filling pressures.
UVR Exposure Sensitizes Keratinocytes to DNA Adduct Formation (2009)

UV radiation (UVR) and exposure to tobacco smoke, a source of polycyclic aromatic hydrocarbons (PAH), have been linked to skin carcinogenesis. UVR-mediated activation of the aryl hydrocarbon receptor (AhR) stimulates the transcription of CYP1A1 and CYP1B1, which encode proteins that convert PAH to genotoxic metabolites. We determined whether UVR exposure sensitized human keratinocytes to PAH-induced DNA adduct formation. UVR exposure induced CYP1A1 and CYP1B1 in HaCaT cells, an effect that was mimicked by photooxidized tryptophan (aTRP) and FICZ, a component of aTRP. UVR exposure or pretreatment with aTRP or FICZ also sensitized cells to benzo(a)pyrene (B[a]P)-induced DNA adduct formation. alphaNF, an AhR antagonist, suppressed UVR-, aTRP-, and FICZ-mediated induction of CYP1A1 and CYP1B1 and inhibited B[a]P-induced DNA adduct formation. Treatment with 17-AAG, an Hsp90 inhibitor, caused a marked decrease in levels of AhR; inhibited UVR-, aTRP-, and FICZ-mediated induction of CYP1A1 and CYP1B1; and blocked the sensitization of HaCaT cells to B[a]P-induced DNA adduct formation. FICZ has been suggested to be a physiologic ligand of the AhR that may have systemic effects. Hence, studies of FICZ were also carried out in MSK-Leuk1 cells, a model of oral leukoplakia. Pretreatment with alpha-naphthoflavone or 17-AAG blocked FICZ-mediated induction of CYP1A1 and CYP1B1, and suppressed the increased B[a]P-induced DNA adduct formation. Collectively, these results suggest that sunlight may activate AhR signaling and thereby sensitize cells to PAH-mediated DNA adduct formation. Antagonists of AhR signaling may have a role in the chemoprevention of photocarcinogenesis.
Activation of the innate immune system by the endogenous ligand hyaluronan (2008)

Hyaluronan activates innate alloimmune responses and subsequently influences adaptive alloimmunity. Improving our understanding of the nature of endogenous innate ligands that activate alloimmunity may lead to improved therapeutics in organ transplantation.
String-Wise Information Flow Tracking against Script Injection Attacks (2009)

Nowadays, security of Web applications faces a threat of script injection attacks. DTP (dynamic taint propagation) and DIFT (dynamic information flow tracking) have been established as powerful techniques to detect script injection attacks. However current DTP/DIFT systems still suffer from tradeoff between false positives and negatives.This paper proposes string-wise information flow tracking, SWIFT. SWIFT traces memory access of program execution, detects string access and distinguishes string operations from other memory access. Current DTP/DIFT systems propagate taint from source to destination operands. Instead of that, SWIFT propagates taint information under string operations. This makes SWIFT provide a better accuracy on detection of script injection attacks than current DTP/DIFT systems.We implemented SWIFT on an IA-32 emulator Bochs, executed typical string operations and made injection attacks to some real-world Web applications with known vulnerabilities. As a result, SWIFT shows a high precision in our security experiments.
Biochemical and Functional Characterization of Germ Line <i>KRAS</i> Mutations (2007)

Germ line missense mutations in HRAS and KRAS and in genes encoding molecules that function up- or downstream of Ras in cellular signaling networks cause a group of related developmental disorders that includes Costello syndrome, Noonan syndrome, and cardiofaciocutaneous syndrome. We performed detailed biochemical and functional studies of three mutant K-Ras proteins (P34R, D153V, and F156L) found in individuals with Noonan syndrome and cardiofaciocutaneous syndrome. Mutant K-Ras proteins demonstrate a range of gain-of-function effects in different cell types, and biochemical analysis supports the idea that the intrinsic Ras guanosine nucleotide triphosphatase (GTPase) activity, the responsiveness of these proteins to GTPase-activating proteins, and guanine nucleotide dissociation all regulate developmental programs in vivo.
The effect of zinc-protamine-glucagon in acute pancreatitis. (1980)

A double blind study testing the effect of long-acting zinc-protamine-glucagon (7.5 mg every 12 hours for 4--5 days) was carried out in acute pancreatitis. There were 32 patients in ZP-glucagon- and 39 patients in the placebo group. The results show that glucagon had a slightly favourable effect on the general clinical course of the disease but they do not give enough evidence for routine use of glucagon in pancreatitis.
Synthesis of trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,2-b ][1]benzothiophene, a potentially carcinogenic metabolite of sulfur heterocycle phenanthro[3,2-b ][1]benzothiophene (2001)

The present study describes the synthesis of trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,2-b][1]benzothiophene (3), which is a potential proximate carcinogen of the environmentally occurring potent carcinogen phenanthro[3,2-b][1]benzothiophene (1). Three approaches were investigated for the synthesis of 3. In the first approach, the diarylalkene 9, which was prepared by the Wittig reaction of ylide 7 and aldehyde 8, was subjected to an oxidative photocyclization reaction to produce a mixture of compounds from which 5, a synthetic precursor to 3, was obtained only in trace amounts. The major cyclized product was 10. The second approach entailed the Suzuki cross-coupling reaction of 2-(dihydroxyboryl)-5-methoxybenzaldehyde (12) with 3-bromodibenzothiophene (11) to produce 13 in 92% yield. The aldehyde function of 13 was elongated with trimethylsulfonium iodide in the presence of KOH to generate the ethylene oxide 14, which, after methanesulfonic acid treatment, produced a 1 ∶ 1 mixture of 3-methoxyphenanthro[3,2-b][1]benzothiophene (6) and 3-methoxyphenanthro[1,2-b][1]benzothiophene (15). Only the undesired compound 15 could be isolated in pure form by extracting the mixture with hot ethanol, leaving behind a 7 ∶ 3 mixture of 6 and 15. In the third approach, the Wittig reaction of 7 with 2-bromo-5-methoxybenzaldehyde (16) produced 17 predominantly as the Z-isomer in quantitative yield. Cyclodehydrobromination of 17 with KOH–quinoline at elevated temperature produced a mixture from which 6 and 3-methoxyphenanthro[3,4-b][1]benzothiophene (18) were easily separated by column chromatography in 23 and 51% yields, respectively. The intermediate 6 was conveniently processed to 3 following the reaction sequence: methoxy phenol→o-quinone→dihydrodiol. A relatively polar dihydrodiol obtained by similar processing of the mixture of 6 and 15 was identified as 3.
Lymphomatoid papulosis with possible progression to lymphoma: T-cell subpopulations as prognostic indicators. (1984)

Some of the factors thought to be responsible for rectal prolapse in children are reviewed. In the United Kingdom management has in the past been conservative. It is suggested that children should be treated at an early stage by means of an injection of phenol in almond oil, in order to reduce the discomfort of recurrent manipulative reductions of the prolapse in the child and alleviate the anxiety of the parents. In 18 cases treated during the past 3 years a single injection performed under general anaesthesia, as a day case, was successful in preventing further prolapse of the rectum.
Application of Experimental Design to the Conductivity Optimization for Waterborne Polyurethane Electrolytes (1999)

The optimization of conductivity for waterborne polyurethane (WPU) electrolytes and liquid electrolytes was studied by using response surface methodology (RSM) coupled with central composition design (CCD). Alternating current impedance and differential scanning calorimeter experiments were performed to obtain the ionic conductivities and thermal properties of WPU electrolytes, respectively. By means of RSM and CCD, the effect of lithium perchlorate (LiClO4) concentration and ratio of propylene carbonate (PC) to ethylene carbonate on conductivity for WPU electrolytes has been systematically investigated. Through this methodology, an empirical equation of conductivity for WPU electrolytes is obtained via regression analysis to be plotted as contour diagrams, facilitating the straight examination of experimental results. The contour plots show that the maximum conductivity (ca. 0.22 mS cm-1) can be obtained at a LiClO4 concentration of 0.9 M and a PC content of 37.5%. To confirm this optimum, three additional experiments were performed and the average conductivity at room temperature is 0.282 mS cm-1.
Cipher instruction search attack on the bus-encryption security microcontroller DS5002FP (1998)

A widely used bus-encryption microprocessor is vulnerable to a new practical attack. This type of processor decrypts on-the-fly while fetching code and data, which are stored in RAM only in encrypted form. The attack allows easy, unauthorized access to the decrypted memory content.
The Infecting Dose of<i>Chlamydia muridarum</i>Modulates the Innate Immune Response and Ascending Infection (2004)

Murine vaginal infection with the obligate intracellular bacterium Chlamydia muridarum is commonly used as a model for ascending Chlamydia infections of the human female genital tract. Gamma interferon-producing Th1 cells, in concert with other mononuclear infiltrates, primarily mediate antichlamydial immunity. However, many factors modify this response, including the bacterial load. To investigate the manner in which the inoculating dose of C. muridarum modulates a genital infection, we measured innate and adaptive cell numbers, CD4+ lymphocyte cytokine profile, chemokine expression, course of infection, and pathological sequelae in genital tracts of BALB/c mice infected with doses of C. muridarum ranging from 10(4) to 10(7) inclusion-forming units. We found that the influx of both innate and adaptive immune cells responded similarly in the lower genital tract (cervical-vaginal tissues) and upper genital tract (oviduct tissues) to increasing inoculating doses. However, cells expressing the innate markers Gr-1 and CD11c were affected to a greater degree by increasing dose than lymphocytes of the adaptive immune response (Th1, CD4+, CD8+, CD19+), resulting in a change in the balance of innate and adaptive cell numbers to favor innate cells at higher infecting doses. Surprisingly, we detected greater numbers of viable chlamydiae in the oviducts at lower inoculating doses, and the number of organisms appeared to directly correlate with hydrosalpinx formation after both primary infection and repeat infection. Taken together, these data suggest that innate immune cells contribute to control of ascending infection.
The <i>nop-1</i> gene of <i>Neurospora crassa</i> encodes a seven transmembrane helix retinal-binding protein homologous to archaeal rhodopsins (1999)

Opsins are a class of retinal-binding, seven transmembrane helix proteins that function as light-responsive ion pumps or sensory receptors. Previously, genes encoding opsins had been identified in animals and the Archaea but not in fungi or other eukaryotic microorganisms. Here, we report the identification and mutational analysis of an opsin gene, nop-1, from the eukaryotic filamentous fungus Neurospora crassa. The nop-1 amino acid sequence predicts a protein that shares up to 81.8% amino acid identity with archaeal opsins in the 22 retinal binding pocket residues, including the conserved lysine residue that forms a Schiff base linkage with retinal. Evolutionary analysis revealed relatedness not only between NOP-1 and archaeal opsins but also between NOP-1 and several fungal opsin-related proteins that lack the Schiff base lysine residue. The results provide evidence for a eukaryotic opsin family homologous to the archaeal opsins, providing a plausible link between archaeal and visual opsins. Extensive analysis of Deltanop-1 strains did not reveal obvious defects in light-regulated processes under normal laboratory conditions. However, results from Northern analysis support light and conidiation-based regulation of nop-1 gene expression, and NOP-1 protein heterologously expressed in Pichia pastoris is labeled by using all-trans [3H]retinal, suggesting that NOP-1 functions as a rhodopsin in N. crassa photobiology.
CROSS-VALIDATORY CHOICE FOR THE NUMBER OF PRINCIPAL COMPONENTS IN PRINCIPAL COMPONENT REGRESSION (1996)

We propose a cross-validatory method to choose the number of principal components in principal component regression based on the predicted error sum of squares. In the process of computation, we propose to use an approximation formula using a linear approximation based on the perturbation expansion. A numerical example is given to show the validity of the proposed method.
An Effective Approach for Coupling Direct Analysis in Real Time with Atmospheric Pressure Drift Tube Ion Mobility Spectrometry (2014)

Drift tube ion mobility spectrometry (DTIMS) has evolved as a robust analytical platform routinely used for screening small molecules across a broad suite of chemistries ranging from food and pharmaceuticals to explosives and environmental toxins. Most modern atmospheric pressure IM detectors employ corona discharge, photoionization, radioactive, or electrospray ion sources for efficient ion production. Coupling standalone DTIMS with ambient plasma-based techniques, however, has proven to be an exceptional challenge. Device sensitivity with near-ground ambient plasma sources is hindered by poor ion transmission at the source-instrument interface, where ion repulsion is caused by the strong electric field barrier of the high potential ion mobility spectrometry (IMS) inlet. To overcome this shortfall, we introduce a new ion source design incorporating a repeller point electrode used to shape the electric field profile and enable ion transmission from a direct analysis in real time (DART) plasma ion source. Parameter space characterization studies of the DART DTIMS setup were performed to ascertain the optimal configuration for the source assembly favoring ion transport. Preliminary system capabilities for the direct screening of solid pharmaceuticals are briefly demonstrated.
100 million words of English (1993)

A description of the background, nature and prospects of the British National Corpus project
Antisense Technology: Selection and Delivery of Optimally Acting Antisense Oligonucleotides (1998)

AbstractAntisense technology has increasingly become a reality. It's objective is simple: to inhibit gene expression in a highly sequence-specific and selective manner. The technology has come to encompass three distinct strategies: antigene and antisense oligonucleotides (ODNs) and ribozymes. The antigene strategy relies on short, synthetic ODNs to form triple helical structures with duplex DNA to interfere with gene expression at the level of transcription, whereas antisense ODNs and ribozymes are designed to interfere with gene expression at the level of single stranded RNA (pre-mRNA or mRNA). Antisense ODNs simply rely on the fidelity of Watson:Crick base pairing interactions to hybridize (bind) to the target RNA and inhibit translation by several putative mechanisms including steric hindrance of ribosomal read-through or, depending on the ODN chemistry, by activation of RNaseH to selectively destroy the RNA component of the duplex. In contrast, ribozymes are RNA-based "antisense" oligonucleotides which exhibit the intrinsic capability of catalyzing the hydrolytic destruction of the target RNA within the RNA:ribozyme duplex. The catalytic activity of ribozymes is achieved by having a defined motif of core ribonucleotides which are not antisense (i.e. complementary) to the targeted mRNA molecules. Several RNA motifs are catalytic but the most commonly studied is the hammerhead motif (Symons, 1992; Akhtar and Rossi, 1996). Hammerhead Ribozymes and antisense ODNs are currently undergoing clinical evaluation as potential therapeutic agents in the treatment of HIV-infection in AIDS patients and also for a variety of cancers and inflammatory disorders (Akhtar and Agrawal, 1997; Narayanan and Akhtar, 1996). Although ribozymes and antisense molecules can be delivered as genes (gene therapy approach), in this article I will largely discuss the exogenous delivery of synthetic antisense ODNs and ribozymes.
Periodic heart rate decelerations in premature infants (2010)

The pacemaking system of the heart is complex; a healthy heart constantly integrates and responds to extracardiac signals, resulting in highly complex heart rate patterns with a great deal of variability. In the laboratory and in some pathological or age-related states, however, dynamics can show reduced complexity that is more readily described and modeled. Reduced heart rate complexity has both clinical and dynamical significance - it may provide warning of impending illness or clues about the dynamics of the heart's pacemaking system. In this paper, we describe simple and interesting heart rate dynamics that we have observed in premature human infants - reversible transitions to large-amplitude periodic oscillations - and we show that the appearance and disappearance of these periodic oscillations can be described by a simple mathematical model, a Hopf bifurcation.
An Event-Driven Workflow Engine for Service-based Business Systems (2006)

This paper discusses a novel implementation of a workflow engine that supports service-based applications. The applications are defined according to the GAT model, which is an event-based programming model using conditional guards to determine when both normal and exception-handling activities are to be executed. We propose implementation techniques for key features of GAT. These include implementing control flow based on the evaluation of guards, the management and distribution of events, and enforcing atomicity across the evaluation of guards and the execution of the corresponding activities. We have built an engine following this approach which uses available technologies to support translating GAT models into executable applications
224. 5-Alkylacridines. Part I. Synthesis of 5-methylacridine and certain substituted analogues (1958)

A. Campbell, C. S. Franklin, E. N. Morgan and D. J. Tivey, J. Chem. Soc., 1958, 1145 DOI: 10.1039/JR9580001145