gebhart/patrepeval huggingface dataset:
Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene (2007)

The IFN-induced resistance factor Mx1 is a critical component of innate immunity against influenza A viruses (FLUAV) in mice. Animals carrying a wild-type Mx1 gene (Mx1(+/+)) differ from regular laboratory mice (Mx1(-/-)) in that they are highly resistant to infection with standard FLUAV strains. We identified an extraordinary variant of the FLUAV strain, A/PR/8/34 (H1N1) (designated hvPR8), which is unusually virulent in Mx1(+/+) mice. hvPR8 was well controlled in Mx1(+/+) but not Mx1(-/-) mice provided that the animals were treated with IFN before infection, indicating that hvPR8 exhibits normal sensitivity to growth restriction by Mx1. hvPR8 multiplied much faster than standard PR8 early in infection because of highly efficient viral gene expression in infected cells. Studies with reassortant viruses containing defined genome segments of both hvPR8 and standard PR8 demonstrated that the HA, neuraminidase, and polymerase genes of hvPR8 all contributed to virulence, indicating that efficient host cell entry and early gene expression renders hvPR8 highly pathogenic. These results reveal a surprisingly simple concept of how influenza viruses may gain virulence and illustrate that high speed of virus growth can outcompete the antiviral response of the infected host.
Directed mutagenesis and barnase-barstar recognition (1993)

Directed mutagenesis has been applied to the cloned genes of barnase and barstar, the extracellular ribonuclease of Bacillus amyloliquefaciens and its intracellular inhibitor, to locate residues involved in the mutual recognition of these two proteins. Arg59 and His102 of barnase and Asp35 and Asp39 of barstar have been so identified. With both Cys40 and Cys82 mutated to alanines, barstar is still produced in high yield and is functional both in vitro and in vivo. Methods devised for determining relative and absolute dissociation coefficients for various combinations of mutant and wild-type proteins have allowed us to determine a dissociation coefficient for the complex of wild-type barnase and barstar of about 10(-13) M, with off and on rate constants of 10(-5) s-1 and 10(8) M-1 s-1, respectively.
RLIP76 and Cancer (2008)

RLIP76 is a multifunctional membrane protein that transports glutathione conjugates of electrophilic compounds and other xenobiotics including chemotherapy agents out of cells. The protein is overexpressed in lung carcinomas, ovarian carcinomas, and melanomas. The protein also binds Ral and participates in mitotic spindle function, clathrin-dependent endocytosis, and triggers GTPase-activating protein activity. It is found throughout the cell, in membrane, cytosol, and the nucleus, and is known to shift between these compartments in response to stress. Loss of RLIP76 by antibody or antisense therapy is associated with increased sensitivity to radiation and chemotherapy. Conversely, liposomally delivered RLIP may treat poisoning and wounds.
High-Temperature Conversion of SO2 to SO3: Homogeneous Experiments and Catalytic Effect of Fly Ash from Air and Oxy-fuel Firing (2014)

The reaction of SO2 with fly ash in the presence of O2 and H2O involves a series of reactions that lead to the formation of SO3 and eventually H2SO4. Homogeneous experiments were conducted to evaluate the effects of the procedural variables, i.e., temperature, gas concentrations, and residence time, on the post-combustion conversion of SO2 to SO3. The results were compared to existing global kinetics and found to be dependent upon SO2, O2, residence time, and temperature and independent of H2O content. For a residence time of 1 s, temperatures of about 900 °C are needed to have an observable conversion of SO2 to SO3. Literature suggested that the conversion of SO2 to SO3 is dependent upon the iron oxide content of the fly ash. Experiments using three different fly ash samples from Australian sub-bituminous coals were used to investigate the catalytic effects of fly ash on SO2 conversion to SO3 at a temperature range of 400–1000 °C. It was observed that fly ash acts as a catalyst in the formation of SO3, with the largest conversion occurring at 700 °C. A homogeneous reaction at 700 °C, without fly ash present, converted 0.10% of the available SO2 to SO3. When fly ash was present, the conversion increased to 1.78%. The catalytic effect accounts for roughly 95% of the total conversion. Average SO3/SO2 conversion values between fly ash derived from air and oxy-fuel firing and under different flue gas environments were found to be similar.
Use of Gabapentin in the Treatment of Neuropathic Pain (2000)

Gabapentin appears to be effective in treating various neuropathic pain disorders. Gabapentin may have advantages over current therapies, such as a favorable safety profile and lack of drug interactions; however, cost issues and limited experience may limit the use of gabapentin as a first-line option.
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation (2005)

Interleukin (IL)-23 is a heterodimeric cytokine composed of a unique p19 subunit, and a common p40 subunit shared with IL-12. IL-12 is important for the development of T helper (Th)1 cells that are essential for host defense and tumor suppression. In contrast, IL-23 does not promote the development of interferon-gamma-producing Th1 cells, but is one of the essential factors required for the expansion of a pathogenic CD4(+) T cell population, which is characterized by the production of IL-17, IL-17F, IL-6, and tumor necrosis factor. Gene expression analysis of IL-23-driven autoreactive T cells identified a unique expression pattern of proinflammatory cytokines and other novel factors, distinguishing them from IL-12-driven T cells. Using passive transfer studies, we confirm that these IL-23-dependent CD4(+) T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity.
Site-specific DNA-antibody conjugates for specific and sensitive immuno-PCR (2012)

Antibody conjugates are widely used as diagnostics and imaging reagents. However, many such conjugates suffer losses in sensitivity and specificity due to nonspecific labeling techniques. We have developed methodology to site-specifically conjugate oligonucleotides to antibodies containing a genetically encoded unnatural amino acid with orthogonal chemical reactivity. These oligobody molecules were used in immuno-PCR assays to detect Her2(+) cells with greater sensitivity and specificity than nonspecifically coupled fragments, and can detect extremely rare Her2(+) cells in a complex cellular environment. Such designed antibody-oligonucleotide conjugates should provide sensitive and specific reagents for diagnostics, as well as enable other unique applications based on oligobody building blocks.
Novel Electron-Rich Bulky Phosphine Ligands Facilitate the Palladium-Catalyzed Preparation of Diaryl Ethers (1999)

A general method for the palladium-catalyzed formation of diaryl ethers is described. Electron-rich, bulky aryldialkylphosphine ligands, in which the two alkyl groups are either tert-butyl or 1-adamantyl, are the key to the success of the transformation. A wide range of electron-deficient, electronically neutral and electron-rich aryl bromides, chlorides, and triflates can be combined with a variety of phenols with the use of sodium hydride or potassium phosphate as base in toluene at 100 °C. The bulky yet basic nature of the phosphine ligand is thought to be responsible for increasing the rate of reductive elimination of the diaryl ether from palladium.
Variant human breast tumor estrogen receptor with constitutive transcriptional activity. (1991)

Since progesterone receptor (PgR) is normally induced by estrogen, breast cancer lacking estrogen receptor (ER) would also be expected to lack PgR. However, a small percentage of breast cancers are ER- yet PgR+. These tumors might possess an ER which is defective in estrogen binding but is still functional in stimulating estrogen-responsive genes such as PgR. We have now detected such a variant, lacking exon 5 of the hormone-binding domain, using complementary DNA amplified by the polymerase chain reaction. This variant was the predominate ER RNA expressed in three ER-/PgR+ tumors. Furthermore, the variant ER constitutively activates transcription of a normally estrogen-dependent gene construct in yeast cells. The variant ER could explain the expression of PgR in certain tumors and have therapeutic implications.
Role of interleukin‐6 in cardiomyocyte/cardiac fibroblast interactions during myocyte hypertrophy and fibroblast proliferation (2005)

The process of cardiac hypertrophy is considered to involve two components: that of cardiac myocyte (CM) enlargement and cardiac fibroblast (CF) proliferation. The interleukin-6 (IL-6) family cytokines have been implicated in a variety of cellular and molecular interactions between myocytes and non-myocytes (NCMs), which in turn have important roles in the development of cardiac hypertrophy. In the study of these interactions, we previously detected very high levels of IL-6 in supernatants of a "dedifferentiated model" of adult ventricular CMs cultured with CFs. In the present study, we have used this in vitro coculture system to examine how IL-6 is involved in the interactions between CMs and CFs during CM hypertrophy and CF proliferation. IL-6 and its signal transducer, 130-kDa glycoprotein (gp130), were detected by immunostaining cultured CMs and CFs with anti-IL-6 or anti-gp130 antibodies. Addition of anti-IL-6 or anti-gp130 antagonist antibodies into CM/CF cocultures induced a significant decrease in expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (beta-MHC) in CMs. The presence of IL-6 antagonist also resulted in a decrease in the surface area of 12-day-old CMs cultured with CFs or in the presence of fibroblast conditioned medium (FCM), and decreased fibroblast proliferation in CM/CF cocultures, particularly in the presence of a gp130 antagonist. The results also show that angiotensin II (AngII) is mainly secreted by CFs and induces IL-6 secretion in CMs cultured with CFs or with FCM. In addition, the effects of IL-6 on cardiomyocyte hypertrophy and fibroblast proliferation were inhibited by addition of the AT-1 receptor antagonist, losartan. These results suggest that IL-6 contributes significantly to CM hypertrophy by an autocrine pathway and to fibroblast proliferation by a paracrine pathway and that these effects could be mediated by AngII.
An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis (2013)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that targets motor neurons, leading to paralysis and death within a few years of disease onset. While several genes have been linked to the inheritable, or familial, form of ALS, much less is known about the cause(s) of sporadic ALS, which accounts for ~90% of ALS cases. Due to the clinical similarities between familial and sporadic ALS, it is plausible that both forms of the disease converge on a common pathway and, therefore, involve common factors. Recent evidence suggests the Cu,Zn-superoxide dismutase (SOD1) protein to be one such factor that is common to both sporadic and familial ALS. In 1993, mutations were uncovered in SOD1 that represent the first known genetic cause of familial ALS. While the exact mechanism of mutant-SOD1 toxicity is still not known today, most evidence points to a gain of toxic function that stems, at least in part, from the propensity of this protein to misfold. In the wild-type SOD1 protein, non-genetic perturbations such as metal depletion, disruption of the quaternary structure, and oxidation, can also induce SOD1 to misfold. In fact, these aforementioned post-translational modifications cause wild-type SOD1 to adopt a "toxic conformation" that is similar to familial ALS-linked SOD1 variants. These observations, together with the detection of misfolded wild-type SOD1 within human post-mortem sporadic ALS samples, have been used to support the controversial hypothesis that misfolded forms of wild-type SOD1 contribute to sporadic ALS pathogenesis. In this review, we present data from the literature that both support and contradict this hypothesis. We also discuss SOD1 as a potential therapeutic target for both familial and sporadic ALS.
Neuromodulation 10 years on: how widely should we use this technique in bladder dysfunction? (2009)

Neuromodulation has a role in the treatment of nonobstructed urinary retention and overactive bladder syndrome, especially when accompanied by urgency incontinence. There are a number of unanswered questions remaining, however, which will need to be addressed to maximize its benefit.
D-Altritol Nucleic Acids (ANA): Hybridisation Properties, Stability, and Initial Structural Analysis (1999)

Oligonucleotides composed of a phosphorylated D-altritol backbone (see diagram) with nucleobases in the 2′-position, hybridise strongly and sequence selectively with RNA in an antiparallel way (dsANA>ANA:RNA>ANA:DNA). Complexes between ANA and RNA or DNA are more stable than between HNA and natural oligonucleotides. A hexamer dsANA hybrid gives a ΔTm per modification of +10.2 °C relative to an identical dsDNA sequence. CD spectral analysis indicates that ANA complexes are very similar to the A-form dsRNA duplex.
A compact SAW-less multiband WCDMA/GPS receiver front-end with translational loop for input matching (2011)

This paper describes a compact SAW-less receiver front-end design targeting multiband multimode GSM/EDGE/WCDMA/GPS applications. Using a translational loop for input matching, the inductor-free receiver achieves high OOB lin earity and low NF at low power consumption.
Identification of a locus involved in the utilization of iron by Haemophilus influenzae (1994)

Haemophilus influenzae has an absolute requirement for heme for aerobic growth. This organism can satisfy this requirement by synthesizing heme from iron and protoporphyrin IX (PPIX). H. influenzae type b (Hib) strain DL42 was found to be unable to form single colonies when grown on a medium containing free iron and PPIX in place of heme. In contrast, the nontypeable H. influenzae (NTHI) strain TN106 grew readily on the same medium. A genomic library from NTHI strain TN106 was used to transform Hib strain DL42, and recombinants were selected on a medium containing iron and PPIX in place of heme. A recombinant plasmid with an 11.5-kb NTHI DNA insert was shown to confer on Hib strain DL42 the ability to grow on iron and PPIX. Nucleotide sequence analysis revealed that this NTHI DNA insert contained three genes, designated hitA, hitB, and hitC, which encoded products similar to the SfuABC proteins of Serratia marcescens, which have been shown to constitute a periplasmic binding protein-dependent iron transport system in this enteric organism. The NTHI HitA protein also was 69% identical to the ferric-binding protein of Neisseria gonorrhoeae. Inactivation of the cloned NTHI hitC gene by insertion of an antibiotic resistance cartridge eliminated the ability of the recombinant plasmid to complement the growth deficiency of Hib DL42. Construction of an isogenic NTHI TN106 mutant lacking a functional hitC gene revealed that this mutation prevented this strain from growing on a medium containing iron and PPIX in place of heme. This NTHI hitC mutant was also unable to utilize either iron bound to transferrin or iron chelates. These results suggest that the products encoded by the hitABC genes are essential for the utilization of iron by NTHI.
Cooperative transcription factor associations discovered using regulatory variation (2011)

Regulation of gene expression at the transcriptional level is achieved by complex interactions of transcription factors operating at their target genes. Dissecting the specific combination of factors that bind each target is a significant challenge. Here, we describe in detail the Allele Binding Cooperativity test, which uses variation in transcription factor binding among individuals to discover combinations of factors and their targets. We developed the ALPHABIT (a large-scale process to hunt for allele binding interacting transcription factors) pipeline, which includes statistical analysis of binding sites followed by experimental validation, and demonstrate that this method predicts transcription factors that associate with NFκB. Our method successfully identifies factors that have been known to work with NFκB (E2A, STAT1, IRF2), but whose global coassociation and sites of cooperative action were not known. In addition, we identify a unique coassociation (EBF1) that had not been reported previously. We present a general approach for discovering combinatorial models of regulation and advance our understanding of the genetic basis of variation in transcription factor binding.
Differential tubulogenic and branching morphogenetic activities of growth factors: implications for epithelial tissue development. (1995)

At least two kidney epithelial cell lines, the Madin-Darby canine kidney (MDCK) and the murine inner medullary collecting duct line mIMCD-3, can be induced to form branching tubular structures when cultured with hepatocyte growth factor (HGF) plus serum in collagen I gels. In our studies, whereas MDCK cells remained unable to form tubules in the presence of serum alone, mIMCD-3 cells formed impressive branching tubular structures with apparent lumens, suggesting the existence of specific factors in serum that are tubulogenic for mIMCD-3 cells but not for MDCK cells. Since normal serum does not contain enough HGF to induce tubulogenesis, these factors appeared to be substances other than HGF. This was also suggested by another observation: when MDCK cells or mIMCD-3 cells were cocultured under serum-free conditions with the embryonic kidney, both cell types formed branching tubular structures similar to those induced by HGF; however, only in the case of MDCK cells could this be inhibited by neutralizing antibodies against HGF. Thus, the embryonic kidney produces growth factors other than HGF capable of inducing tubule formation in the mIMCD-3 cells. Of a number of growth factors examined, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) were found to be tubulogenic for mIMCD-3 cells. Whereas only HGF was a potent tubulogenic factor for MDCK cells, HGF, TGF-alpha, and EGF were potent tubulogenic factors for mIMCD-3 cells. Nevertheless, there were marked differences in the capacity of these tubulogenic factors to induce tubulation as well as branching events in those tubules that did form (HGF >> TGF-alpha > EGF). Thus, at least three different growth factors can induce tubulogenesis and branching in a specific epithelial cell in vitro (though to different degrees), and different epithelial cells that are capable of forming branching tubular structures demonstrate vastly different responses to tubulogenic growth factors. The results are discussed in the context of branching morphogenesis during epithelial tissue development.
Seed Treatment with a Fungal or a Bacterial Antagonist for Reducing Corn Damping-off Caused by Species of Pythium and Fusarium (1997)

Bioassays were conducted under greenhouse conditions to test the efficacy of antagonists applied to corn (Zea mays) seed for protection against seed rot and seedling damping-off at 18 and 25°C in a field soil artificially infested with a combination of Pythium ultimum, P. arrhenomanes, and Fusarium graminearum. Biomass of Gliocladium virens isolates Gl-3 or Gl-21, Trichoderma viride isolate Tv-1, or peat-based slurry of Burkholderia cepacia isolates Bc-B, Bc-T, or Bc-1 was coated individually onto corn seeds in one test, and Gl-3 or Bc-B at four inoculum levels was used in another test. Seed treatments with most of the biocontrol agents, as well as with the fungicide captan, significantly (P ≤ 0.05) increased seedling stand, plant height and fresh weight, and decreased root rot severity compared with untreated seeds in pathogen-infested soil. Coating seeds with the biocontrol fungus G. virens isolate Gl-3 was the most effective treatment, resulting in greater (P ≤ 0.05) seedling stand, plant height, and fresh weight, and lower (P ≤ 0.05) severity of root rot than those parameters from seeds treated with captan or other antagonists at both temperatures. The results from the seeds treated with Gl-3 were similar to those of untreated seeds in noninfested soil. In treatments with Bc-1, Bc-T, Bc-B, or Tv-1, incubation temperature affected plant emergence, root rot severity, plant height, and fresh weight (P ≤ 0.01). Conversely, in seeds coated with Gl-3 or Gl-21, these parameters were similar at both temperatures. The minimum number of propagules needed per corn seed to obtain plant emergence comparable to that from captan-treated seeds was between 10<sup>4</sup> and 10<sup>5</sup> CFU for Gl-3 and >10<sup>8</sup> for Bc-B. When propagules of Gl-3 were applied at a rate >10<sup>6</sup> CFU per seed, seedling emergence was greater (P ≤ 0.05) than that from captan-treated seeds.
Involvement of Dopamine in Development of Hypertension in Spontaneously Hypertensive Rat: Effect of Carbidopa, Inhibitor of Peripheral DOPA Decarboxylase (1987)

The demonstration of acceleration of hypertension was investigated in spontaneously hypertensive rats (SHR) treated with carbidopa, inhibitor of peripheral dopa decarboxylase. Oral administration of carbidopa to young SHR for 4 weeks accelerated significantly (P less than 0.05) development of hypertension as compared to SHR treated with vehicle. Urinary excretion of dopamine (DA) (P less than 0.01) and renal content of DA (P less than 0.02) were significantly decreased by carbidopa treatment. Urinary excretion of sodium (P less than 0.05) was significantly decreased and renal content of norepinephrine (NE) (P less than 0.01) was significantly increased by carbidopa. Urinary excretion of NE and epinephrine (E) did not change during the experimental period. Negative correlation between systolic blood pressure and urinary excretion of sodium (P less than 0.05) or dopamine (P less than 0.01) and positive correlation between systolic blood pressure and renal content of NE (P less than 0.05) were significantly observed in both groups of SHR treated with carbidopa and with vehicle for 4 weeks. These results suggest that decreased DA biosynthesis in peripheral tissues accelerates development of hypertension mediated by decrease of natriuresis and enhanced release of NE in the kidneys of SHR. DA plays an important role in regulation of blood pressure, and reduced dopaminergic mechanisms enhance blood pressure in SHR.
Oligoaminudeoside phosphoramidates. Oligomeilzation of dimers of 3′-amino-3′-deoxy-nucleotides (GC and CG) in aqueous solution (1987)

The self-complementary 5'-phosphorylated dinucleoside 3' (N)----5' (P)-linked phosphoramidates with sequence GC (8a), CG (8b) and the tetranucleoside triphosphoramidate with sequence GCGC (10a) and CGCG (10b) have been synthesized and characterized by physicochemical and enzymatic methods. The dinucleosides 8a or 8b oligomerize in aqueous solution in the presence of a water-soluble carbodiimide. This process is efficient and regiospecific. In the case of GC it produces alternating 3' (N)----5' (P)-linked phosphoramidates up to 15 dimeric units in length with a yield in excess of 70%. The oligomerization of the CG isomer is much less efficient. The mechanism of oligomerization is discussed.