gebhart/patrepeval huggingface dataset:
Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry (1996)

A panel of primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates that infected several CD4+ T-cell lines, including MT-2 and C8166, were tested for infection of blood-derived macrophages. Infectivity titers for C8166 cells and macrophages demonstrated that primary SI strains infected macrophages much more efficiently than T-cell line-adapted HIV-1 strains such as LAI and RF. These primary SI strains were therefore dual-tropic. Nine biological clones of two SI strains, prepared by limiting dilution, had macrophage/C8166 infectivity ratios similar to those of their parental viruses, indicating that the dual-tropic phenotype was not due to a mixture of non-SI/macrophage-tropic and SI/T-cell tropic viruses. We tested whether the primary SI strains used either Lestr (fusin) or CCR5 as coreceptors. Infection of cat CCC/CD4 cells transiently expressing Lestr supported infection by T-cell line-adapted strains including LAI, whereas CCC/CD4 cells expressing CCR5 were sensitive to primary non-SI strains as well as to the molecularly cloned strains SF-162 and JR-CSF. Several primary SI strains, as well as the molecularly cloned dual-tropic viruses 89.6 and GUN-1, infected both Lestr+ and CCR5+ CCC/CD4 cells. Thus, these viruses can choose between Lestr and CCR5 for entry into cells. Interestingly, some dual-tropic primary SI strains that infected Lestr+ cells failed to infect CCR5+ cells, suggesting that these viruses may use an alternative coreceptor for infection of macrophages. Alternatively, CCR5 may be processed or presented differently on cat cells so that entry of some primary SI strains but not others is affected.
Inelastic tunneling spectroscopy of magnetic tunnel junctions based on CoFeB∕MgO∕CoFeB with Mg insertion layer (2006)

Magnetic tunnel junctions (MTJs) based on textured MgO barriers have thus far shown the highest tunneling magnetoresistance (TMR) at room temperature. In contrast to traditional magnetic tunnel junctions, it appears that the large TMR observed in these systems arises from a type of coherent tunneling in which the symmetry of the Bloch state wave functions plays a critical role. We have fabricated MTJs with artificial asymmetric barriers by depositing a thin layer of Mg of varying thickness (0–10 Å) prior to the growth of the MgO barrier into otherwise identical CoFeB∕MgO∕CoFeB MTJs. The inelastic tunnel spectrum shows magnon and phonon excitation peaks similar to traditional Al2O3 barriers, and an additional peak at about 300 meV. The conventional interpretation that this peak corresponds to density of states of the s electrons in the ferromagnetic electrodes, however, does not apply in the MgO system.
Effect of Formalin, Acetone, and RNAlater Fixatives on Tissue Preservation and Different Size Amplicons by Real-Time PCR from Paraffin-Embedded Tissue (2004)

RNA recovered from paraffin-embedded tissue has been reported to be a suitable substrate for polymerase chain reaction. During tissue fixation and paraffin embedding, RNA undergoes degradation, but with certain restrictions, it can be used for gene expression studies. At the same time, formalin-fixed, paraffin embedded histopathology archives contain an unestimable collection, which could be analyzed to investigate changes in mRNA expression in pathologic processes. To decide for future tissue conservation of pathology samples, it would be reasonable to satisfy both histologic and molecular biologic needs. The effect of three different fixation methods, RNAlater (SIGMA R 0901, St Louis, MO), acetone, and formalin, were compared by histology, immunohistochemistry, and real-time PCR. To assess tissue structure preservation and antigenicity, hematoxylin-eosin staining and immunohistochemistry were performed; to assess RNA quality, RNA was extracted and the transcription of different amplicon sizes (121, 225, 406 bp for GAPDH; 166, 310, 536 bp for beta globin) were examined on human endometrium samples. The most adequate tissue preservation was found in case of formalin fixation, while there were no significant differences in the three fixatives' yields for various size real-time PCR amplicons. Longer amplicons (above approximately 225 bp) have limited use for gene expression studies, while shorter amplicons could give more reliable results.
Thy/Liv-SCID-Hu Mice Implanted with Human Intestine: An in Vivo Model for Investigation of Mucosal Transmission of HIV (1997)

Mucosal transmission is a major route by which individuals become infected with HIV. Investigation into the mechanism by which mucosal transmission of HIV occurs would be greatly facilitated by the development of a small animal model infectible with HIV by the mucosal route. We have previously described a SCID-hu mouse model, in which human thymic and liver tissues are implanted under both kidney capsules (thy/liv-SCID-hu mice), which are populated in the periphery with high numbers of human T cells and that develop disseminated HIV-1 infection after intraperitoneal injection. To expand further the usefulness of the thy/liv-SCID-hu mouse as a model for studying mucosal transmission of HIV, thy/liv-SCID-hu mice were subcutaneously implanted with human intestinal tissue in a manner that maintained the lumen. Four months later, the histological appearance of the implanted intestine resembled that of normal human bowel tissue and the lamina propria was populated with human T cells. Six weeks after introduction of HIV into the lumen of the intestinal implant, the mice developed disseminated HIV infection. Scattered HIV-infected cells were detected in the lamina propria of the implant, indicating that HIV infection in these mice was mediated by transmission of the virus across the mucosa of the human intestinal implant. Thus, our modified thy/liv-SCID-hu mice transplanted with human bowel tissue should provide a novel model for investigating mucosal transmission of HIV.
Comparative Evaluation of the Indirect Immunoperoxidase Test for the Serodiagnosis of Rickettsial Disease (1988)

An indirect immunoperoxidase test was compared with an indirect fluorescent antibody test and the Weil-Felix OXK test for serodiagnosis of scrub typhus by measuring the rickettsial antigen specific activity of IgG, IgM, and whole globulin. Acute and convalescent sera from 50 Rickettsia tsutsugamushi isolate-positive scrub typhus patients and from 45 febrile patients diagnosed as having diseases other than scrub typhus were tested. The receiver operating characteristic for each test showed that the indirect immunoperoxidase and indirect fluorescent antibody tests were more sensitive and specific than the Weil-Felix test using convalescent and acute as well as paired sera. The indirect immunoperoxidase test showed no cross-reactivity when R. tsutsugamushi antigen was tested against sera collected from patients living outside the scrub typhus-endemic area with diseases other than scrub typhus. The indirect immunoperoxidase and indirect fluorescent antibody tests were comparable in measured response to R. tsutsugamushi, R. typhi, and TT-118 (spotted fever group) antigen. Thus the indirect immunoperoxidase test represents a sensitive, specific, reproducible, and practical semiquantitative test for rickettsial disease diagnosis.
Effects of Dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease (1997)

A placebo-controlled crossover design, with each treatment period lasting 6 weeks, was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzhemer's disease who were refusing food. Eleven patients completed both study periods; one patient who died of a heart attack 2 weeks before the end of the study was also included in the analysis. The study was terminated in 3 patients: one developed a grand mal seizure and 2 developed serious intercurrent infections. Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods. Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first. Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria, somnolence and tiredness, but did not require discontinuation of therapy. These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer's disease.
Free-running enzymatic oligonucleotide synthesis for data storage applications (2018)

Abstract Here we present preliminary results for a method of oligodeoxynucleotide synthesis using terminal deoxynucleotidyl transferase (TdT) to generate mixed base homopolymer runs of defined sequence. In a process we have termed Free-Running Synthesis (FRS), we allow TdT to freely add multiple bases of a given monomer. With this method, homopolymeric runs can be used for writing DNA in a data storage capacity, where a stretch of A’s, for example, will be read as a single base, and the transitions between successive homopolymer runs encodes information. As a proof-of-concept, we demonstrate homopolymer additions of A, C and T onto the 3’ end of a 22 base initiator strand.
Partition function and base pairing probabilities of RNA heterodimers (2006)

RNA has been recognized as a key player in cellular regulation in recent years. In many cases, non-coding RNAs exert their function by binding to other nucleic acids, as in the case of microRNAs and snoRNAs. The specificity of these interactions derives from the stability of inter-molecular base pairing. The accurate computational treatment of RNA-RNA binding therefore lies at the heart of target prediction algorithms. The standard dynamic programming algorithms for computing secondary structures of linear single-stranded RNA molecules are extended to the co-folding of two interacting RNAs. We present a program, RNAcofold, that computes the hybridization energy and base pairing pattern of a pair of interacting RNA molecules. In contrast to earlier approaches, complex internal structures in both RNAs are fully taken into account. RNAcofold supports the calculation of the minimum energy structure and of a complete set of suboptimal structures in an energy band above the ground state. Furthermore, it provides an extension of McCaskill's partition function algorithm to compute base pairing probabilities, realistic interaction energies, and equilibrium concentrations of duplex structures. RNAcofold is distributed as part of the Vienna RNA Package, http://www.tbi.univie.ac.at/RNA/ . Stephan H. Bernhart – berni@tbi.univie.ac.at
Suppression of mutations in the core of the Tetrahymena ribozyme by spermidine, ethanol and by substrate stabilization (1994)

We have previously described a collection of mutations in conserved residues of the core of the Tetrahymena self-splicing intron. Most of these single base substitutions have less than 10% of the activity of their parental intron derivative [Couture, S., et al., (1990) J. Mol. Biol., 215, 345-358]. We examined the effect of two agents known to stabilize RNA structure, spermidine and ethanol, on the activity of many of these mutant RNAs. In the presence of either 5 mM spermidine or 20% ethanol most substitution mutations were partially or completely suppressed. These conditions also increased the temperature optima of both wild-type and mutant ribozymes. In addition, we find that mutations are also suppressed by a high concentration of GTP, a substrate in the reaction which is bound specifically by the intron. Thus we observe a general suppression of mutations in an RNA enzyme (ribozyme) by spermidine, ethanol and by substrate stabilization. These results are consistent with the idea that most mutations destabilize the folded structure of the ribozyme and can be suppressed by any of a variety of stabilizing influences.
Semirational design of active tumor suppressor p53 DNA binding domain with enhanced stability (1998)

We have designed a p53 DNA binding domain that has virtually the same binding affinity for the gadd45 promoter as does wild-type protein but is considerably more stable. The design strategy was based on molecular evolution of the protein domain. Naturally occurring amino acid substitutions were identified by comparing the sequences of p53 homologues from 23 species, introducing them into wild-type human p53, and measuring the changes in stability. The most stable substitutions were combined in a multiple mutant. The advantage of this strategy is that, by substituting with naturally occurring residues, the function is likely to be unimpaired. All point mutants bind the consensus DNA sequence. The changes in stability ranged from +1.27 (less stable Q165K) to -1.49 (more stable N239Y) kcal mol-1, respectively. The changes in free energy of unfolding on mutation are additive. Of interest, the two most stable mutants (N239Y and N268D) have been known to act as suppressors and restored the activity of two of the most common tumorigenic mutants. Of the 20 single mutants, 10 are cancer-associated, though their frequency of occurrence is extremely low: A129D, Q165K, Q167E, and D148E are less stable and M133L, V203A and N239Y are more stable whereas the rest are neutral. The quadruple mutant (M133LV203AN239YN268D), which is stabilized by 2.65 kcal mol-1 and Tm raised by 5.6 degreesC is of potential interest for trials in vivo.
Choline deficiency: A cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation (1995)

Patients receiving long-term total parenteral nutrition (TPN) develop hepatic steatosis as a complication. Our previous studies have shown this to be caused, at least in part, by choline deficiency. We studied four patients (1 man, 3 women) aged 50 +/- 13 years who had low plasma-free choline concentrations 4.8 +/- 1.7 (normal, 11.4 +/- 3.7 nmol/mL). The patients had received TPN for 9.7 +/- 4.7 years. They received parenteral nutrition solutions containing choline chloride (1 to 4 g/d) for 6 weeks. Abdominal computed tomography (CT) was performed at baseline, biweekly during the choline supplementation, and 4 weeks after discontinuation of choline. During choline administration, the plasma-free choline concentration increased into the normal range within 1 week in all four patients and remained at or above the normal range for all 6 weeks, but decreased back to baseline when choline supplementation was discontinued. Hepatic steatosis resolved completely, as estimated by CT. Liver density increased from -14.2 +/- 22.3 Hounsfield units (HU) to 8.4 +/- 10.3 HU at week 2 (P = .002); 9.6 +/- 10.7 HU at week 4 and 13.1 +/- 7.3 HU at week 6, as determined by the liver-spleen CT number difference obtained by the subtraction of the average spleen CT number (in HU) from the average liver CT number. This improvement continued up to 4 weeks after choline supplementation (13.8 +/- 2.8 HU). Hepatic steatosis was shown to have recurred in one patient after 10 weeks of return to choline-free parenteral nutrition. The hepatic steatosis associated with parenteral nutrition can be ameliorated, and possibly prevented, with choline supplementation. Therefore, choline may be an essential nutrient for patients who require long-term parenteral nutrition.
Physical interaction between the herpes simplex virus type 1 immediate-early regulatory proteins ICP0 and ICP4 (1994)

The herpes simplex virus type 1 immediate-early protein ICP0 enhances expression of a spectrum of viral genes alone and synergistically with ICP4. To test whether ICP0 and ICP4 interact physically, we performed far-Western blotting analysis of proteins from mock-, wild-type-, and ICP4 mutant virus-infected cells with in vitro-synthesized [35S]Met-labeled ICP0 and ICP4 as probes. The ICP4 and ICP0 polypeptides synthesized in vitro exhibited molecular weights similar to those of their counterparts in herpes simplex virus type 1-infected cells, and the in vitro-synthesized ICP4 was able to bind to a probe containing the ICP4 consensus binding site. Far-Western blotting experiments demonstrated that ICP0 interacts directly and specifically with ICP4 and with itself. To further define the interaction between ICP0 and ICP4, we generated a set of glutathione S-transferase (GST)-ICP0 fusion proteins that contain GST and either ICP0 N-terminal amino acids 1 to 244 or 1 to 394 or C-terminal amino acids 395 to 616 or 395 to 775. Using GST-ICP0 fusion protein affinity chromatography and in vitro-synthesized [35S]Met-labeled ICP0 and ICP4, ICP4 was shown to interact preferentially with the fusion protein containing ICP0 C-terminal amino acids 395 to 775, whereas ICP0 interacted efficiently with both the N-terminal GST-ICP0 fusion proteins and the C-terminal GST-ICP0 fusion proteins containing amino acids 395 to 775. Fusion protein affinity chromatography also demonstrated that the C-terminal 235 amino acid residues of ICP4 are important for efficient interaction with ICP0. Collectively, these results reveal a direct and specific physical interaction between ICP0 and ICP4.
Activation of the complement system during immunotherapy with recombinant IL-2. Relation to the development of side effects. (1990)

Therapy with high doses of rIL-2 is complicated by the occurrence of hypotensive reactions and the development of a vascular leakage syndrome (VLS). In four patients, who together received seven cycles of high doses of IL-2 (up to 12 x 10(6) U per m2 per day), and who developed these side effects, we observed an unexpected increase in plasma levels of C3a, indicating activation of the complement system. C3a levels markedly increased during IL-2 therapy from 4 nmol/liter (mean level) before therapy to 23 nmol/liter at the end of the cycle. Activation of C3 occurred via the classical pathway inasmuch as C4a levels also increased during therapy. Mean daily C3a levels correlated with signs of the VLS, such as daily weight gain (p less than 0.001) and albumin levels (inverse correlation, p less than 0.001). In five additional patients, who together received seven cycles of lower doses of IL-2 (2 x 10(6) U per m2 per day) and who did not develop a VLS, only moderate increases in C3a levels (up to 13 nmol/liter) were observed. The highest levels at the first day of the regimen (mean: 7 nmol/liter) occurred 8 h after the IL-2 infusion. Thus, administration of IL-2 induces a dose-dependent activation of the complement system in vivo, which appeared to be related to the development of side effects of this therapy, such as the VLS.
Cross Domain Random Walk for Query Intent Pattern Mining from Search Engine Log (2011)

Understanding search intents of users through their condensed short queries has attracted much attention both in academia and industry. The search intents of users are generally assumed to be associated with various query patterns, such as "MobileName price", where "MobileName" could be any named entity of mobile phone model and this pattern indicates that the user intends to buy a mobile phone. However, discovering the query intent patterns for general search is challenging mainly due to the difficulty in collecting sufficient training data for learning query patterns across a large number of searchable domains. In this work, we propose Cross Domain Random Walk (CDRW) algorithm, which is semi-supervised, to discover the query intent patterns across different domains from search engine click-through log data. Starting with some manually tagged seed queries in one or more independent domains, CDRW takes the query patterns as bridge and propagates the transition probability across domains to collect the query intent patterns among different domains based on the assumption that "users who have similar intent in different but similar domains will have high probability to share similar query patterns across domains". Different from classical random walk algorithms, CDRW walks across different domains to disseminate the shared knowledge in a transfer learning manner. Extensive experiment results on real log data of a commercial search engine well validate the effectiveness and efficiency of the proposed algorithm.
Reversal of epigenetic promoter silencing in Friedreich ataxia by a class I histone deacetylase inhibitor (2016)

Friedreich ataxia, the most prevalent inherited ataxia, is caused by an expanded GAA triplet-repeat sequence in intron 1 of the FXN gene. Repressive chromatin spreads from the expanded GAA triplet-repeat sequence to cause epigenetic silencing of the FXN promoter via altered nucleosomal positioning and reduced chromatin accessibility. Indeed, deficient transcriptional initiation is the predominant cause of transcriptional deficiency in Friedreich ataxia. Treatment with 109, a class I histone deacetylase (HDAC) inhibitor, resulted in increased level of FXN transcript both upstream and downstream of the expanded GAA triplet-repeat sequence, without any change in transcript stability, suggesting that it acts via improvement of transcriptional initiation. Quantitative analysis of transcriptional initiation via metabolic labeling of nascent transcripts in patient-derived cells revealed a >3-fold increase (P < 0.05) in FXN promoter function. A concomitant 3-fold improvement (P < 0.001) in FXN promoter structure and chromatin accessibility was observed via Nucleosome Occupancy and Methylome Sequencing, a high-resolution in vivo footprint assay for detecting nucleosome occupancy in individual chromatin fibers. No such improvement in FXN promoter function or structure was observed upon treatment with a chemically-related inactive compound (966). Thus epigenetic promoter silencing in Friedreich ataxia is reversible, and the results implicate class I HDACs in repeat-mediated promoter silencing.
Regioselective Conjugation of Chitosan with a Laminin-related Peptide, Tyr-Ile-Gly-Ser-Arg, and Evaluation of Its Inhibitory Effect on Experimental Cancer Metastasis. (1999)

A conjugate from the YIGSR peptide and chitosan has been prepared on the basis of a regioselective modification strategy of chitosan, and its antimetastatic activity has been assayed. Chitosan was converted to its organosoluble derivative, 6-O-trityl-chitosan, in 3 steps, and then coupled with the peptide portion containing a spacer amino acid, Ac-Tyr-Ile-Gly-Ser-Arg-beta Ala-OH [beta Ala; beta-alanine]. The product was treated with CHCl2CO2H to afford the desired conjugate, Ac-Tyr-Ile-Gly-Ser-Arg-beta Ala-chitosan, which proved to inhibit the experimental lung metastasis of B16BL6 melanoma cells in mice at lower doses than the parent peptide.