gebhart/patrepeval huggingface dataset:
Specificity of the mouse cytotoxic T lymphocyte response to adenovirus 5. E1A is immunodominant in H-2b, but not in H-2d or H-2k mice (1991)

The Ag specificity and MHC restriction of the CTL response to adenovirus 5 (Ad5) in three strains of mice, C57BL/10 (H-2b), BALB/c (H-2d), and C3H/HeJ (H-2k), were tested. Polyclonal Ad5-specific CTL were prepared by priming mice in vivo with live Ad5 virus followed by secondary in vitro stimulation of the spleen cells with virus-infected syngeneic cells. The Ad5-specific CTL were Db restricted in C57BL/10 and Kk restricted in C3H/HeJ. In BALB/c mice both Kd- and Dd/Ld-restricted CTL were detected. The polyclonal Ad5-specific CTL response in C57BL/10 mice is directed exclusively against the products of the E1A region, which comprises only 5% of the Ad5 genome. In BALB/c mice E1A is at best a very minor target Ag and in C3H/HeJ mice E1A is not recognized at all. Using the H-2 congenic mouse strains B10.BR (H-2k) and C3H.SW (H-2b) it was shown that the immunodominance of E1A is H-2 dependent. The 19-kDa glycoprotein encoded in the E3 region of Ad5, which binds to class I MHC in the endoplasmic reticulum and prevents its translocation to the cell surface, does not affect the specificity of the CTL response in C57BL/10 mice toward E1A. However, it affects the MHC restriction of the Ad5-specific response in BALB/c mice, selectively inhibiting generation of Kd-restricted CTL.
Simple Telemedicine for Developing Regions: Camera Phones and Paper-Based Microfluidic Devices for Real-Time, Off-Site Diagnosis (2008)

This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.
Molecular Cloning and Functional Characterization of a New Modulatory Cyclic Nucleotide-Gated Channel Subunit from Mouse Retina (2000)

Cyclic nucleotide-gated (CNG) channels play a key role in olfactory and visual transduction. Native CNG channels are heteromeric complexes consisting of the principal α subunits (CNG1–3), which can form functional channels by themselves, and the modulatory β subunits (CNG4–5). The individual α and β subunits that combine to form the CNG channels in rod photoreceptors (CNG1 + CNG4) and olfactory neurons (CNG2 + CNG4 + CNG5) have been characterized. In contrast, only an α subunit (CNG3) has been identified so far in cone photoreceptors. Here we report the molecular cloning of a new CNG channel subunit (CNG6) from mouse retina. The cDNA of CNG6 encodes a peptide of 694 amino acids with a predicted molecular weight of 80 kDa. Among the CNG channel subunits, CNG6 has the highest overall similarity to the CNG4 β subunit (47% sequence identity). CNG6 transcripts are present in a small subset of retinal photoreceptor cells and also in testis. Heterologous expression of CNG6 in human embryonic kidney 293 cells did not lead to detectable currents. However, when coexpressed with the cone photoreceptor α subunit, CNG6 induced a flickering channel gating, weakened the outward rectification in the presence of extracellular Ca 2+ , increased the sensitivity for l - cis diltiazem, and enhanced the cAMP efficacy of the channel. Taken together, the data indicate that CNG6 represents a new CNG channel β subunit that may associate with the CNG3 α subunit to form the native cone channel.
Interleukin-9 in Human Myeloid Leukemia Cells (1997)

Here we review our recent data addressing the role of recombinant human (rh) interleukin 9 (IL-9) in acute myeloblastic leukemia (AML). We first evaluated the proliferative response of 3 leukemic cell lines and 32 primary samples from AML patients to IL-9 alone and combined with rh-IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF, c-kit ligand). The colony forming ability of leukemic cells was assessed by a clonogenic assay in methylcellulose, whereas the cell cycle characteristics of the same samples were determined by the acridine-orange (AO) flow cytometric technique and the bromodeoxyuridine (BRDU) incorporation assay. In addition, the terminal deoxynucleotidyl transferase Assay (TDTA) and standard analysis of DNA cleavage by gel electrophoresis were used to evaluate induction or prevention of apoptosis by IL-9. IL-9, used as a single cytokine, at various concentrations stimulated the colony formation of the 3 myeloid cell lines under serum-containing and serum-free conditions and this effect was completely abrogated by anti-IL-9 monoclonal antibodies (MoAbs). When tested on fresh AML samples, optimal concentrations of IL-9 resulted in the increase of the blast colony formation in all the cases studied and was the most effective CSF for promoting leukemic cell growth among those tested in this study including SCF, IL-3, and GM-CSF. The addition of SCF to IL-9 demonstrated an additive or synergistic effect of the 2 cytokines in 5 out of 8 AML cases tested for their CFU-L growth (187 +/- 79 colonies in comparison with 107 +/- 32 CFU-L; p = 0.05). Positive interaction was also observed when IL-9 was combined with IL-3 and GM-CSF. Studies of cell cycle distribution of AML samples demonstrated that IL-9 alone significantly augmented the number of leukemic cells in S-phase in the majority of the cases evaluated. IL-9 and SCF in combination resulted in a remarkable decrease of the G0 cell fraction (38.2 +/- 24% compared to 58.6 +/- 22% of control cultures; p < 0.05) and induced an increase of G1 and S-phase cells. Conversely, neither IL-9 alone nor the combination of IL-9 and SCF had any effect on induction or prevention of apoptosis of leukemic cells. Furthermore, in this study, reverse transcriptase-polymerase chain reaction amplification (RT-PCR) did not show the constitutive expression of IL-9 mRNA in the cell lines and the AML samples studied at diagnosis. In summary, IL-9 may play a role in the development of acute myeloid leukemia by stimulating the proliferation of leukemic cells perhaps through a paracrine growth loop.
Methotrexate pharmacogenomics in rheumatoid arthritis: introducing false-positive report probability (2009)

In this issue of the Journal, Lee and associates [1] investigated the contribution of candidate polymorphisms in folate and purine pathways to disease activity in RA patients treated with low-dose MTX therapy. This cross-sectional study analysis in patients enrolled in the BRASS (Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study) cohort sought to replicate the earlier findings from our group [2-4] as well as those from Leiden University The results clearly illustrate the challenges and difficulties we face when validating associations between low-penetrance genetic polymorphisms and complex phenotypes such as drug response. In particular, the authors establish that the minor allele of rs4673993 in 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase (ATIC, in proxy with a C347G non-synonymous SNP encoding a threonine-to-serine substitution at position 116) is associated with improved clinical status, a finding consistent with the results observed in our US cohort
Neisseria gonorrhoeae bacterioferritin: structural heterogeneity, involvement in iron storage and protection against oxidative stress (1999)

The iron-storage protein bacterioferritin (Bfr) from Neisseria gonorrhoeae strain F62 was identified in cell-free extracts and subsequently purified by column chromatography. Gonococcal Bfr had an estimated molecular mass of 400 kDa by gel filtration; however, analysis by SDS-PAGE revealed that it was composed of 18 kDa (BfrA) and 22 kDa (BfrB) subunits. DNA encoding BfrB was amplified by PCR using degenerate primers derived from the N-terminal amino acid sequence of BfrB and from a C-terminal amino acid sequence of Escherichia coli Bfr. The DNA sequence of bfrA was subsequently obtained by genome walking using single-specific-primer PCR. The two Bfr genes were located in tandem with an intervening gap of 27 bp. A potential Fur-binding sequence (12 of 19 bp identical to the consensus neisserial fur sequence) was located within the 5' flanking region of bfrA in front of a putative -35 hexamer. The homology between the DNA sequences of bfrA and bfrB was 55.7%; the deduced amino acid sequences of BfrA (154 residues) and BfrB (157 residues) showed 39.7% identity, and showed 41.3% and 56.1% identity, respectively, to E. coli Bfr. Expression of recombinant BfrA and BfrB in E. coli strain DH5alpha was detected on Western blots probed with polyclonal anti-E. coli Bfr antiserum. Most Bfrs are homopolymers with identical subunits; however, the evidence presented here suggests that gonococcal Bfr was composed of two similar but not identical subunits, both of which appear to be required for the formation of a functional Bfr. A Bfr-deficient mutant was constructed by inserting the omega fragment into the BfrB gene. The growth of the BfrB-deficient mutant in complex medium was reduced under iron-limited conditions. The BfrB-deficient mutant was also more sensitive to killing by H2O2 and paraquat than the isogenic parent strain. These results demonstrate that gonococcal Bfr plays an important role in iron storage and protection from iron-mediated oxidative stress.
Graft polymers with macromonomers. I. Synthesis from methacrylate‐terminated polystyrene (1982)

Abstract Pure graft polymers having uniform molecular weight polystyrene side chains were prepared by free radical copolymerization of methacrylate‐terminated polystyrene macromonomers (MA‐CROMER) with ethyl acrylate, butyl acrylate, or other suitable monomers. The MACROMER monomer was synthesized by living anionic polymerization under conditions that led to very narrow molecular weight distributions. Very effective end capping produced a material that was highly monofunctional. The graft copolymers were prepared by several techniques such as free radical solution polymerization, by aqueous suspension polymerization which produced beads, or by emulsion reactions which yielded stable latices. Polymerizations were reproducible. High conversion of the MACROMER monomer into pure graft polymers was achieved, and the product was contaminated with only a little homopolymer. The milled and molded phase‐separated graft polymers had optical clarity and physical properties characteristic of polystyrene‐reinforced triblock polymers. Compositions of 20‐30% polystyrene were thermoplastic elastomers with good recovery. When polystyrene contents were increased, the graft products were strong, flexible thermoplastics with well defined yield strengths and increased permanent set. Copolymers of polystyrene macromers with acrylonitrile or vinyl chloride produced transparent polystyrene homopolymer‐free graft polymer products having improved processing over polyacrylonitrile or poly(vinyl chloride) homopolymers.
A Library of Noviosylated Coumarin Analogues (2007)

The DNA gyrase inhibitor, novobiocin, was recently shown to inhibit Hsp90 via a previously unrecognized C-terminal ATP-binding site. Previous structure-activity relationship studies identified key moieties that appear important for Hsp90 inhibitory activity. In an effort to provide a more efficacious lead compound, a parallel library of noviosylated coumarin analogues was prepared.
Evolution of the neoclassical theory (historical review, 1951-1989) (1991)

A historical review is given of the main stages of the development of neoclassic theory starting from its beginning and up to nowadays; the scientists are mentioned who contributed much in the development of the theory. Although almost none of the mathematical expositions are given in the paper, however, the physical nature of new effects and the results obtained in the cited papers are discussed in detail.
Interleukin-6 as a Therapeutic Target in Candidate Inflammatory Diseases (2010)

Interleukin (IL)-6 is a multifunctional cytokine that regulates immune response, inflammation, and hematopoiesis. Although IL-6 plays several important physiological roles, deregulated overproduction of IL-6 causes various clinical symptoms and abnormalities in laboratory test results. Overproduction of IL-6 has been shown to underlie a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA), systemic-onset juvenile idiopathic arthritis (soJIA), and Castleman's disease, as well as malignancies such as multiple myeloma and mesothelioma. Blocking of IL-6 signaling may be therapeutic in diseases characterized by pathological IL-6 overproduction. This review provides an overview of IL-6 as a therapeutic target in candidate inflammatory diseases.
Aging and vascular endothelial function in humans (2011)

Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging.
Methotrexate as the "anchor drug" for the treatment of early rheumatoid arthritis. (2004)

The two major advances over the 1990s in the treatment of rheumatoid arthritis (RA) were a shift in strategy from a "pyramid", in which disease modifying anti-rheumatic drugs (DMARDs) were deferred for several years, to the early aggressive use of DMARDs and widespread acceptance of methotrexate as the DMARD with the most long-term effectiveness and safety. Methotrexate courses are continued far longer than those of any other DMARD, an excellent indicator of greater effectiveness and safety. In one recent series, methotrexate was the first DMARD used in more than 80% of patients with RA. Studies which document the superiority of combinations of methotrexate with biological agents to methotrexate monotherapy select for only a minority of contemporary patients with RA who have severe disease activity and incomplete responses to methotrexate. In one locale, only 5% of patients met criteria for the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy (ATTRACT) trial and only 30% met the criteria for the Early Rheumatoid Arthritis (ERA) trial. In studies comparing methotrexate directly with biological agents, the biological agents have greater efficacy in patients with very severe disease, but the best results are seen in patients who take a combination of methotrexate and biologic agents. These data establish that methotrexate is the anchor drug and probably should be the first DMARD used in the majority of patients with RA at this time.
Quantum generators of random numbers (2021)

Generation of random numbers is a central problem for many applications in the field of information processing, including, e.g., cryptography, in classical and quantum regime, but also mathematical modeling, Monte Carlo methods, gambling and many others. Both, the quality of the randomness and efficiency of the random numbers generation process are crucial for the most of these applications. Software produced pseudorandom bit sequences, though sufficiently quick, do not fulfill required randomness quality demands. Hence, the physical hardware methods are intensively developed to generate truly random number sequences for information processing and electronic security application. In the present paper we discuss the idea of the quantum random number generators. We also present a variety of tests utilized to assess the quality of randomness of generated bit sequences. In the experimental part we apply such tests to assess and compare two quantum random number generators, PQ4000KSI (of company ComScire US) and JUR01 (constructed in Wroclaw University of Science and Technology upon the project of The National Center for Research and Development) as well as a pseudorandom generator from the Mathematica Wolfram package. Finally, we present our new prototype of fully operative miniaturized quantum random generator JUR02 producing a random bit sequence with velocity of 1 Mb/s, which successfully passed standard tests of randomness quality (like NIST and Dieharder tests). We also shortly discuss our former concept of an entanglement-based quantum random number generator protocol with unconditionally secure public randomness verification.
Effects of Resistance Training on the Rate of Muscle Protein Synthesis in Frail Elderly People (2001)

Advancing age is associated with a reduction in skeletal muscle protein, muscle strength, muscle quality, and chemical modifications that may impair protein function. Sarcopenia has been coupled with physical disability, frailty, and a loss of independent function. Using stable isotope tracer methodologies and mass spectrometric detection, we observed: (a) 76-92-year-old physically frail and 62-74-year-old middle-age adults have lower mixed muscle protein synthetic rates than 20-32-year-old men and women; (b) 2 weeks and 3 months of weightlifting exercise increased the synthetic rate of myosin heavy chain (MHC) and mixed muscle proteins to a similar magnitude in frail, middle-age, and young women and men; (c) Serum myostatin-immunoreactive protein levels were elevated in physically frail women and were inversely correlated with lean mass. This suggests that the protein synthetic machinery adapts rapidly to increased contractile activity and that the adaptive response(s) are maintained even in frail elders.
Specific Chromosome Alterations in Fluconazole-Resistant Mutants of Candida albicans (1999)

The exposure of Candida albicans to fluconazole resulted in the nondisjunction of two specific chromosomes in 17 drug-resistant mutants, each obtained by an independent mutational event. The chromosomal changes occurred at high frequencies and were related to the duration of the drug exposure. The loss of one homologue of chromosome 4 occurred after incubation on a fluconazole medium for 7 days. A second change, the gain of one copy of chromosome 3, was observed after exposure for 35 or 40 days. We found that the mRNA levels of ERG11, CDR1, CDR2, and MDR1, the candidate fluconazole resistance genes, remained either the same or were diminished. The lack of overexpression of putative drug pumps or the drug target indicated that some other mechanism(s) may be operating. The fluconazole resistance phenotype, electrophoretic karyotypes, and transcript levels of mutants were stable after growth for 112 generations in the absence of fluconazole. This is the first report to demonstrate that resistance to fluconazole can be dependent on chromosomal nondisjunction. Furthermore, we suggest that a low-level resistance to fluconazole arising during the early stages of clinical treatment may occur by this mechanism. These results support our earlier hypothesis that changes in C. albicans chromosome number is a common means to control a resource of potentially beneficial genes that are related to important cellular functions.
PPARdelta activation enhances skeletal muscle regeneration (2012)

Skeletal muscle relies mostly on its resident progenitor cells, the satellite cells, for postnatal growth and regeneration. Therefore, maintaining proper function and healthy population of satellite cells are critical for the ability of muscle to control damage. Endurance exercise elicits a myriad of adaptive responses in the muscle, including an increase in the satellite cell number. Targeted expression of constitutively active Peroxisome Proliferator-Activated Receptor delta (VP16-PPAR[delta]) in the skeletal muscle mimics endurance training induced fiber type remodeling, including, glycolytic to oxidative fiber type switch and concomitant increase in the running capacity. Currently, however, it is unknown whether transcriptionally directed "endurance exercise training" adaptations by PPAR[delta] in the muscle is sufficient to affect satellite cell homeostasis and function. We herein present that PPAR[delta] activation promotes acceleration of regenerative process after an acute injury. We found that the skeletal muscle specific over-expression of PPAR[delta] induces increase in the satellite cell population. Furthermore, we observed an increase in the number of proliferating cells after injury, leading to an increase in the number of nascent regenerating fibers. Gene expression analyses showed an earlier resolution of inflammatory response and induction of myogenic markers, suggesting that PPAR[delta] actuates temporal shift of the regenerative process. Interestingly, PPAR[delta] promotes myoblast proliferation immediately after the injury, which correlates with strong induction of Notch signaling pathway by PPAR[delta]. Additionally, acute pharmacological activation of PPAR[delta] also promoted efficient restoration of fiber integrity. Collectively, our results demonstrate a new role for PPAR[delta] in skeletal muscle regeneration. Our findings allude to the therapeutic potential of PPAR[delta], not only for the treatment of an acute injury, but also in Notch-dependent aging associated loss of regenerative capacity of the muscle