gebhart/patrepeval huggingface dataset:
Raf and Mitogen-activated Protein Kinase Regulate Stellate Cell Collagen Gene Expression (1996)

Hepatic stellate cells become activated into myofibroblast-like cells during the early stages of hepatic injury associated with fibrogenesis. The subsequent dysregulation of hepatic stellate cell collagen gene expression is a central pathogenetic step during the development of cirrhosis. The cytoplasmic Raf and mitogen-activated protein (MAPK) kinases were found to differentially regulate alpha I(I) collagen gene expression in activated stellate cells. This suggests an unappreciated branch point exists between Raf and MAPK. A MAPK-stimulatory signal was mapped to the most proximal NF-1 and Sp-1 binding domains of the 5'-untranslated region of the collagen gene. A Raf-inhibitory signal was mapped to a further upstream binding domain involving a novel 60-kDa DNA-binding protein (p60). The cell-specific expression and induction of p60 in stellate cells during the early stages of hepatic fibrogenesis in vivo suggest a central role for this pathway during liver injury and stellate cell activation.
Torsion of the left ventricle during the ejection phase in the intact dog (1984)

Torsion of the left ventricle (LV) is associated with rotation of the apex with respect to the base around the long axis of the LV. A mathematical model of LV mechanics, which relates torsion to transmural distribution of fibre shortening, was evaluated with two-dimensional echocardiography in nine anaesthetised closed-chest dogs. Torsion was calculated as the difference between the angles of rotation (radians) of echo-derived transverse cross-section projections of the LV obtained at the mitral valve and low papillary level, divided by the axial distance between these projections measured in a long-axis cross-section, and multiplied by the outer radius in a mid-papillary transverse projection of the LV. A shortening to torsion ratio (STR) was defined as the ratio of inner wall shortening to torsion occurring during ejection. In a series of 11 measurements, each based on frame-to-frame analysis of 15 cardiac cycles, STR was found to be 2.31±0.23 rad−1 (mean±SD), whereas the mathematical model predicted a STR value of 2.4 rad−1 over a wide range of preload, afterload and contractility levels. We conclude that two-dimensional echocardiography validates the presence of torsion in the normal canine left ventricle, as predicted by the model of left ventricular mechanics.
Engineering a unique glycosylation site for site-specific conjugation of haptens to antibody fragments. (1995)

A natural N-linked glycosylation site (Asn-Val-Thr) at amino acid positions 18-20 (Kabat's numbering) was identified in the framework-1 (FR-1) region of the light chain variable (V kappa) domain of a murine anti-B cell lymphoma Ab, LL-2. Our earlier studies demonstrated that no contact between the V kappa-appended oligosaccharide and the Ag binding site was evident, because glycosylation at this site did not affect the Ag binding property of the Ab. By using the murine LL-2 F(ab')2 fragment (which is devoid of constant region-appended oligosaccharide) as substrate, as much as five bifunctional chelator molecules per F(ab')2 fragment could be site specifically conjugated at the V kappa-appended carbohydrate moiety with no reduction in immunoreactivity. The resulting conjugates labeled efficiently with both 90Y and 111In, with no significant effect on Ab affinity. In contrast, conjugation of less than five chelates/Ab fragment randomly at lysine residues resulted in a three- to fivefold reduction in affinity. By a single Arg to Asn mutation, an N-linked glycosylation site similar to that of LL-2 was introduced in the FR-1 segment of a nonglycosylated, humanized anti-carcinoembryonic Ag (CEA) Ab, MN-14 (hMN-14). Glycosylation at the engineered carbohydrate-addition site was demonstrated by SDS-PAGE analysis. Neither glycosylation nor site-specific conjugation of chelate at the V kappa-appended carbohydrate moiety resulted in the loss of immunoreactivity. The glycosylated hMN-14 conjugate labeled efficiently with 90Y.
Personal Area Networks: Changing the Way We Work (2004)

This paper explores how different mobile communications technologies combined together have the potential to significantly change the way we work. Mobile telephony combining satellite and terrestrial cellular systems already has transformed the way people work by allowing “anytime, anywhere” telephone calling and text messaging. However, wireless data has not met the “anytime, anywhere” criteria due to problems with cost, power consumption, compatibility, and bit rate. Not all information should be available anytime, anywhere. The key is to provide information conveniently as quickly and easily as possible when needed and where needed. The evolution of different mobile technologies that consider different needs for timeand space-related information is providing a new capability, personal area networks (PANs), with the potential to change the way we work.
Methotrexate in Childhood Psoriasis (1994)

We treated childhood psoriasis with methotrexate (MTX) in seven children (4 boys, 3 girls) over 7.5 years. Their ages and duration of disease varied from 3.5 to 16 years (mean 12.14 yrs) and 4.8 months to 5 years (mean 2.2 yrs), respectively. Psoriatic erythroderma was seen in three patients, generalized pustular psoriasis in two, recalcitrant psoriasis and psoriatic arthropathy in one each. Pre-MTX liver biopsy performed in 4 children showed grade I changes. Methotrexate was given in a single weekly oral dose of 3.75 to 25 mg (mean 16.6 mg). The duration of treatment necessary to control the disease varied from 6 to 10 weeks (mean 7.9 wks). Total duration of MTX therapy was 31.2 to 46.4 weeks (mean 38.8 wks). Posttherapy disease-free interval ranged between 14.4 and 16.8 weeks (mean 15.5 wks). Follow-up after withdrawal of MTX was 16 to 28 weeks (mean 22.3 wks). Total cumulative MTX dose ranged from 390 to 960 mg (mean 683.6 mg). Side effects were nausea and vomiting in three patients.
Characterization of Methylprednisolone Esters of Hyaluronan in Aqueous Solution:  Conformation and Aggregation Behavior (2005)

Methylprednisolone steroid esters of hyaluronan differing in degree of functionalization and molecular weight were investigated in aqueous solution. Conformation and aggregation phenomena were elucidated by means of circular dichroism, viscometry, rheology, and nuclear magnetic resonance, mainly by (1)H pulsed field gradient (PFG) NMR, which allows the determination of the diffusion coefficient of the species under investigation. The functionalization of hyaluronan with the steroid induces a reduction of the molecular volume, as a consequence of intramolecular hydrophobic interactions. For concentrated samples we have observed the coexistence of unimolecular collapsed chains and of aggregates, the latter disappearing upon dilution. The methylprednisolone ester of lower molecular weight hyaluronan has a larger molecular volume than its higher molecular weight analogue, even though still smaller than the underivatized polymer. This effect can be explained with the reduced flexibility of the polymer backbone probably impairing intramolecular interactions.
PRODH mutations and hyperprolinemia in a subset of schizophrenic patients (2002)

The increased prevalence of schizophrenia among patients with the 22q11 interstitial deletion associated with DiGeorge syndrome has suggested the existence of a susceptibility gene for schizophrenia within the DiGeorge syndrome chromosomal region (DGCR) on 22q11. Screening for genomic rearrangements of 23 genes within or at the boundaries of the DGCR in 63 unrelated schizophrenic patients and 68 unaffected controls, using quantitative multiplex PCR of short fluorescent fragments (QMPSF), led us to identify, in a family including two schizophrenic subjects, a heterozygous deletion of the entire PRODH gene encoding proline dehydrogenase. This deletion was associated with hyperprolinemia in the schizophrenic patients. In addition, two heterozygous PRODH missense mutations (L441P and L289M), detected in 3 of 63 schizophrenic patients but in none among 68 controls, were also associated with increased plasma proline levels. Segregation analysis within the two families harboring respectively the PRODH deletion and the L441P mutation showed that the presence of a second PRODH nucleotide variation resulted in higher levels of prolinemia. In two unrelated patients suffering from severe type I hyperprolinemia with neurological manifestations, we identified a homozygous L441P PRODH mutation, associated with a heterozygous R453C substitution in one patient. These observations demonstrate that type I hyperprolinemia is present in a subset of schizophrenic patients, and suggest that the genetic determinism of type I hyperprolinemia is complex, the severity of hyperprolinemia depending on the nature and number of hits affecting the PRODH locus.
Ambient temperature rapid SARA ATRP of acrylates and methacrylates in alcohol–water solutions mediated by a mixed sulfite/Cu(ii)Br2 catalytic system (2013)

The new generation of catalytic systems for Controlled/“Living” Radical Polymerization (CLRP) of vinyl monomers should be non-toxic, inexpensive and provide fast polymerizations in environmentally friendly media. Herein, we report the successful ambient temperature ATRP of several vinyl monomers (MA, n-BA, MMA and DMAEMA) catalyzed by inorganic sulfites (Na2S2O4 and Na2S2O5) and small amounts of a Cu(II)Br2/Me6TREN system in alcohol–water mixtures. The controlled character of ATRP of acrylates and methacrylates was confirmed by the linear increase of molecular weights with monomer conversion, narrow molecular weight distributions (Mw/Mn ∼ 1.05) and by reinitiation experiments (copolymerization and chain extension). 1H NMR and MALDI-TOF analyses confirmed the molecular structure and chain-end functionality of the obtained polymers. ATRP of MA using this novel catalytic system in alcohol–water mixtures with multifunctional Br-based initiators provides 4 and 6 arm star polyacrylates in a controlled manner without any observable gel formation. The data presented open up the possibility of using fast ATRP catalyzed by inorganic sulfites (approved by FDA as food and beverage additives) in solvents that are inexpensive, eco-friendly and widely used in chemical industrial processes.
Surfaces with holes in them: new plasmonic metamaterials (2005)

In this paper we explore the existence of surface electromagnetic modes in corrugated surfaces of perfect conductors. We analyse two cases: one-dimensional arrays of grooves and two-dimensional arrays of holes. In both cases we find that these structures support surface bound states and that the dispersions of these modes have strong similarities with the dispersion of the surface plasmon polariton bands of real metals. Importantly, the dispersion relation of these surface states is mainly dictated by the geometry of the grooves or holes and these results open the possibility of tailoring the properties of these modes by just tuning the geometrical parameters of the surface.
In vivo evidence suggesting a role for purine‐catabolizing enzymes in the pathogenesis of cisplatin‐induced nephrotoxicity in rats and effect of erdosteine against this toxicity (2004)

The aim of this experimental study was to investigate the possible role of adenosine deaminase (AD) and xanthine oxidase (XO) in the pathogenesis of cisplatin-induced nephrotoxicity and the effect of erdosteine in decreasing the toxicity. The intraperitoneal injection of cisplatin (7 mg kg(-1) body weight) induced a significant increase in plasma creatinine level and blood urea nitrogen (BUN), and plasma and damaged renal tissue activities of AD and XO in rats. Co-treatment with erdosteine (10 mg kg(-1)day(-1)) attenuated the increase in the plasma creatinine and BUN levels, and significantly prevented the increase in tissue and plasma AD and XO activities (P<0.05). The results of this study revealed that XO and AD may play an important role in the pathogenesis of cisplatin-induced nephrotoxicity. The potent free radical scavenger erdosteine may have protective potential in this process and it will become a promising drug in the prevention of this undesired side-effect of cisplatin, but further studies are needed to illuminate the exact protection mechanism of erdosteine against cisplatin-induced nephrotoxicity.
Antibody-dependent enhancement of severe dengue disease in humans (2017)

For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.
Are turns required for the folding of ribonuclease T1? (1996)

Ribonuclease T1 (RNase T1) is a small, globular protein of 104 amino acids for which extensive thermodynamic and structural information is known. To assess the specific influence of variations in amino acid sequence on the mechanism for protein folding, circularly permuted variants of RNase T1 were constructed and characterized in terms of catalytic activity and thermodynamic stability. The disulfide bond connecting Cys-2 and Cys-10 was removed by mutation of these residues to alanine (C2, 10A) to avoid potential steric problems imposed by the circular permutations. The original amino-terminus and carboxyl-terminus of the mutant (C2, 10A) were subsequently joined with a tripeptide linker to accommodate a reverse turn and new termini were introduced throughout the primary sequence in regions of solvent-exposed loops at Ser-35 (cp35S1), Asp-49 (cp49D1), Gly-70 (cp70G1), and Ser-96 (cp96S1). These circularly permuted RNase T1 mutants retained 35-100% of the original catalytic activity for the hydrolysis of guanylyl(3'-->5')cytidine, suggesting that the overall tertiary fold of these mutants is very similar to that of wild-type protein. Chemical denaturation curves indicated thermodynamic stabilities at pH 5.0 of 5.7, 2.9, 2.6, and 4.6 kcal/mol for cp35S1, cp49D1, cp70G1, and cp96S1, respectively, compared to a value of 10.1 kcal/mol for wild-type RNase T1 and 6.4 kcal/mol for (C2, 10A) T1. A fifth set of circularly permuted variants was attempted with new termini positioned in a tight beta-turn between Glu-82 and Gln-85. New termini were inserted at Asn-83 (cp83N1), Asn-84 (cp84N1), and Gln-85 (cp85Q1). No detectable amount of protein was ever produced for any of the mutations in this region, suggesting that this turn may be critical for the proper folding and/or thermodynamic stability of RNase T1.
Biochemistry of Interferons and Their Actions (1982)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Generalized Iterative Scaling for Log-Linear Models (1972)

Say that a probability distribution $\{p_i; i \in I\}$ over a finite set $I$ is in "product form" if (1) $p_i = \pi_i\mu \prod^d_{s=1} \mu_s^{b_si}$ where $\pi_i$ and $\{b_{si}\}$ are given constants and where $\mu$ and $\{\mu_s\}$ are determined from the equations (2) $\sum_{i \in I} b_{si} p_i = k_s, s = 1, 2, \cdots, d$; (3) $\sum_{i \in I} p_i = 1$. Probability distributions in product form arise from minimizing the discriminatory information $\sum_{i \in I} p_i \log p_i/\pi_i$ subject to (2) and (3) or from maximizing entropy or maximizing likelihood. The theory of the iterative scaling method of determining (1) subject to (2) and (3) has, until now, been limited to the case when $b_{si} = 0, 1$. In this paper the method is generalized to allow the $b_{si}$ to be any real numbers. This expands considerably the list of probability distributions in product form which it is possible to estimate by maximum likelihood.
Developing Novel Oncolytic Adenoviruses through Bioselection (2003)

Mutants of human adenovirus 5 (Ad5) with enhanced oncolytic activity were isolated by using a procedure termed bioselection. Two mutants, ONYX-201 and ONYX-203, were plaque purified from a pool of randomly mutagenized Ad5 that was repeatedly passaged in the human colorectal cancer cell line HT29, and they were subsequently characterized. ONYX-201 and ONYX-203 replicated more rapidly in HT29 cells than wild-type Ad5, and they lysed HT29 cells up to 1,000-fold more efficiently. The difference was most profound when cells were infected at a relatively low multiplicity of infection, presumably due to the compounding effects of multiple rounds of infection. This enhanced cytolytic activity was observed not only in HT29 cells but also in many other human cancer cell lines tested. In contrast, the cytotoxicity of the bioselected mutants in a number of normal primary human cells was similar to that of wild-type Ad5, thus enhancing the therapeutic index (cytotoxicity in tumor cells versus that in normal cells) of these oncolytic agents. Both ONYX-201 and -203 contain seven single-base-pair mutations when compared with Ad5, four of which were common between ONYX-201 and -203. The mutation at nucleotide 8350, shared by both mutant viruses, was shown to be essential for the observed phenotypes. This mutation was mapped to the i-leader region of the major late transcription unit, resulting in the truncation of 21 amino acids from the C terminus of the i-leader protein. This work demonstrates that bioselection is a powerful tool for developing novel tumor-selective oncolytic viruses. Other potential applications of this technology are discussed.
Detection of Chemical Warfare-Related Species on Complex Aerosol Particles Deposited on Surfaces Using an Ion Trap-Based Aerosol Mass Spectrometer (2007)

A new type of aerosol mass spectrometer was developed by minimal modification of an existing commercial ion trap to analyze the semivolatile components of aerosols in real time. An aerodynamic lens-based inlet system created a well-collimated particle beam that impacted into the heated ionization volume of the commercial ion trap mass spectrometer. The semivolatile components of the aerosols were thermally vaporized and ionized by electron impact or chemical ionization in the source. The nascent ions were extracted and injected into the ion trap for mass analysis. The utility of this instrument was demonstrated by identifying semivolatile analytes in complex aerosols. This study is part of an ongoing effort to develop methods for identifying chemical species related to CW agent exposure. Our efforts focused on detection of CW-related species doped on omnipresent aerosols such as house dust particles vacuumed from various surfaces found in any office building. The doped aerosols were sampled directly into the inlet of our mass spectrometer from the vacuumed particle stream. The semivolatile analytes were deposited on house dust and identified by positive ion chemical ionization mass spectrometry up to 2.5 h after deposition. Our results suggest that the observed semivolatile species may have been chemisorbed on some of the particle surfaces in submonolayer concentrations and may remain hours after deposition. This research suggests that identification of trace CW agent-related species should be feasible by this technique.
A zinc(ii) metal–organic framework based on triazole and dicarboxylate ligands for selective adsorption of hexane isomers (2011)

A three-dimensional (3D) metal-organic framework {[Zn(2)(HBDC)(2)(dmtrz)(2)]·guest}(n) with pcu net has been solvothermally synthesized, which shows selective adsorption of linear and monobranched hexane isomers over a dibranched one.
Environmental Monitoring for Biological Threat Agents Using the Autonomous Pathogen Detection System with Multiplexed Polymerase Chain Reaction (2008)

We have developed and field-tested a now operational civilian biodefense capability that continuously monitors the air in high-risk locations for biological threat agents. This stand-alone instrument, called the Autonomous Pathogen Detection System (APDS), collects and selectively concentrates particles from the air into liquid samples and analyzes the samples using multiplexed PCR amplification coupled with microsphere array detection. During laboratory testing, we evaluated the APDS instrument's response to Bacillus anthracis and Yersinia pestis by spiking the liquid sample stream with viable spores and cells, bead-beaten lysates, and purified DNA extracts. APDS results were also compared to a manual real-time PCR method. Field data acquired during 74 days of continuous operation at a mass-transit subway station are presented to demonstrate the specificity and reliability of the APDS. The U.S. Department of Homeland Security recently selected the APDS reported herein as the first autonomous detector component of their BioWatch antiterrorism program. This sophisticated field-deployed surveillance capability now generates actionable data in one-tenth the time of manual filter collection and analysis.
[Production and proinflammatory activity of tumor necrosis factor alpha in the glomerulus]. (1995)

The production and the effects of tumor necrosis factor alpha (TNF alpha) have been studied in isolated glomeruli and cultured glomerular cells from animal or human origin. Glomeruli from rats injected with E. coli lipopolysaccharide (LPS) and glomeruli exposed to LPS in vitro release TNF alpha into the medium. The glomerular cells responsible for TNF alpha synthesis are mesangial cells. Production of TNF alpha is controlled by other locally produced mediators. Prostaglandin E2 and interleukin-10 are inhibitory. Hydroxyl radicals stimulate the transformation of the transmembrane form of TNF alpha into its soluble form which is secreted into the medium. TNF alpha acts on its producing cells and on the neighbouring cells. It induces contraction of mesangial cells, increases the synthesis of a variety of local mediators including prostaglandins, platelet-activating factor and chemotactic agents, particularly interleukin-8. Synthesis of this cytokine implies activation of tyrosine kinase and of transcription factors, essentially NFkB. Taken together, these results suggest that TNF alpha plays a marked role in the development of glomerular injury and incite us to search for treatments inhibiting its synthesis and its effects.