gebhart/patrepeval huggingface dataset:
Amelioration of Retinal Photic Injury in Albino Rats by Dimethylthiourea (1990)

Light-induced formation of oxygen free radicals has been proposed as the underlying mechanism of photic retinal injury. We investigated the role of hydroxyl radical in retinal photic injury by treating dark-adapted albino rats with intraperitoneal dimethylthiourea 3 hours before exposure to intense fluorescent light. Dimethylthiourea is a specific antioxidant against hydroxyl radical. We demonstrated that dimethylthiourea penetrates well into retinal tissue and has a half-life of approximately 19 hours. Morephologic differences between the control and dimethylthiurea-treated rats were not remarkable 6 hours after light exposure, but they became significant 6 and 14 days after light exposure. Morphometric studies showed that there was significantly better preservation of photoreceptor nuclei in dimethylthiourea-treated rats 6 and 14 days after light exposure. Rhodopsin levels were significantly higher in the dimethylthiourea-treated rats 6 hours and 14 days after light exposure, while rhodopsin levels were comparable in the control and dimethylthiourea-treated rats 6 days after exposure. The differences in morphometry and rhodopsin levels between the control and dimethylthiourea-treated rats were statistically significant in relationship to dimethylthiourea treatment. The superior and temporal retinal quadrants appeared most vulnerable to photic injury in control rats 6 and 14 days after light exposure. These findings indicate that dimethylthiourea ameliorates retinal photic injury, and that hydroxyl radical plays an important role in mediating retinal photic injury.
Homogeneous hydrogenation of aqueous hydrogen carbonate to formate under mild conditions with water soluble rhodium(I)- and ruthenium(II)-phosphine catalysts (2000)

Water-soluble rhodium(I)- and ruthenium(II)–tertiary phosphine complexes with meta-monosulphonated triphenylphosphine (TPPMS) and 1,3,5-triaza-7-phosphaadamantane (PTA) as ligands catalyze the hydrogenation of aqueous HCO3− to HCO2− under mild conditions. No amine additive is needed for good turnovers. CO2 accelerates the reactions with [RhCl(TPPMS)3] catalyst; however, it slightly inhibits the reductions catalyzed by [RuCl2(TPPMS)2]. Bicarbonate formed in the reaction of limestone with aqueous CO2 can also be used as starting material for formate production. Copyright © 2000 John Wiley & Sons, Ltd.
Regulated translation of listeriolysin O controls virulence of Listeria monocytogenes (2006)

Summary Listeria monocytogenes is an intracytosolic bacterial pathogen that escapes from the phagosome using a secreted cytolysin, listeriolysin O (LLO). In the host cytosol, LLO activity is minimized to prevent pore formation in the host plasma membrane; premature lysis of the infected host cell exposes the bacteria to extracellular immune defences of the host and is detrimental to infection. Here we identified nucleotide substitutions in the coding sequence of the LLO gene ( hly ) that did not alter the protein sequence, yet caused over‐production of LLO, cytotoxicity and loss of virulence. These phenotypes were independent of the promoter and, under conditions in which the mutants produced more LLO protein than wild type, levels of hly mRNA were similar. Finally, negative regulation of LLO was maintained even when bacteria were engineered to produce elevated levels of the wild‐type hly transcript. Together, our data demonstrate that translational regulation of LLO is critical for L. monocytogenes pathogenesis.
Cromolyn Sodium: Fitting an Old Friend into Current Asthma Treatment (2005)

Cromolyn sodium (Intal) has been available in the United States to treat asthma for more than 30 years. Its clinical efficacy in patients with mild or moderate persistent asthma is well documented, and its extensive clinical record of safety remains unique among antiasthma medications. The history of cromolyn sodium complements the science behind current understanding of asthma pathophysiology. Cromolyn sodium was the first nonsteroid, antiasthma drug that blocked chemical mediator release at the cellular level. However, the younger generation of health care providers may not be familiar with the medication due to the plethora of antiasthma agents that have recently become available. This review reexamines the role of cromolyn sodium (now available as an HFA aerosol) in the treatment of asthma.
Analyzing Airway Inflammation with Chemical Biology: Dissection of Acidic Mammalian Chitinase Function with a Selective Drug-like Inhibitor (2011)

Acidic mammalian chitinase (AMCase) is produced in the lung during allergic inflammation and asthma, and inhibition of enzymatic activity has been considered as a therapeutic strategy. However, most chitinase inhibitors are nonselective, additionally inhibiting chitotriosidase activity. Here, we describe bisdionin F, a competitive AMCase inhibitor with 20-fold selectivity for AMCase over chitotriosidase, designed by utilizing the AMCase crystal structure and dicaffeine scaffold. In a murine model of allergic inflammation, bisdionin F-treatment attenuated chitinase activity and alleviated the primary features of allergic inflammation including eosinophilia. However, selective AMCase inhibition by bisdionin F also caused dramatic and unexpected neutrophilia in the lungs. This class of inhibitor will be a powerful tool to dissect the functions of mammalian chitinases in disease and represents a synthetically accessible scaffold to optimize inhibitory properties in terms of airway inflammation.
Analog and Digital Communication Systems (1979)

New edition of an introductory text that balances theoretical foundations with practical design. Reorganization and updates in this edition include the section on digital communications as well as design applications and computer exercises: many graphs are prepared and formulas solved using MATLAB...
A biophysical implementation of a bidirectional graph search algorithm to solve multiple goal navigation tasks (2005)

The model presented here extends formal analysis (Hasselmo et al., Neural Networks, 15, pp. 689-707, 2002b) and abstract modelling (Gorchetchnikov and Hasselmo, Neurocomputing, 44-46, pp. 423-427, 2002a) of interactions within the hippocampal area (or other cortical areas), which can be flexibly used to navigate toward any arbitrary goal or multiple goals that change on a trial-by-trial basis. The algorithm is a version of a bidirectional breadth-first graph search implemented in simulated neurons using two flows of neural activity. The new model changes the continuous firing rate neuronal representations (Gorchetchnikov and Hasselmo 2002a) to more detailed compartmental versions with realistic parameters, while preserving the qualitative properties analysed previously (Hasselmo et al., 2002b, Gorchetchnikov and Hasselmo 2002a). The case of multiple goals being present in the environment is studied in this paper. The first set of simulations tests the algorithm in the selection of the closest goal. A small difference in distance between the simulated animal and different goals is sufficient for a correct selection. The second set of simulations studies the behaviour of the model when the goals have different saliences. A small salience-based difference between firing rates of the cells providing goal-related input to the model is sufficient for the selection of a more salient goal. This behaviour was tested in three types of environments: a linear track, a T-maze and an open field. Further investigation of quantitative properties of the model should allow it to handle cases when the exact location of the goal is uncertain.
A Synthetic Peptide Vaccine Directed against the 2β2–2β3 Loop of Domain 2 of Protective Antigen Protects Rabbits from Inhalation Anthrax (2010)

The current vaccines for anthrax in the United States and United Kingdom are efficacious in the two most accepted animal models of inhalation anthrax, nonhuman primates and rabbits, but require extensive immunization protocols. We previously demonstrated that a linear determinant in domain 2 of Bacillus anthracis protective Ag (PA) is a potentially important target for an epitope-specific vaccine for anthrax, as Abs specific for this site, referred to as the loop-neutralizing determinant (LND), neutralize lethal toxin in vitro, yet are virtually absent in PA-immunized rabbits. In this study, we evaluated the immunogenicity and protective efficacy in rabbits of multiple antigenic peptides (MAPs) consisting of aa 304-319 from the LND of PA colinearly synthesized at the C terminus (T-B MAP) or N terminus (B-T MAP) with a heterologous T cell epitope from Plasmodium falciparum. Immunogenicity studies demonstrated that both MAPs elicited toxin-neutralizing Ab in rabbits. To evaluate the MAPs as potential anthrax vaccines, we immunized groups of rabbits (n = 7) with each MAP in Freund's adjuvant and then exposed all rabbits to a 200-LD(50) challenge with aerosolized spores of B. anthracis Ames strain. All seven rabbits immunized with the B-T MAP and 89% (six of seven) of rabbits immunized with the T-B MAP survived the spore challenge. Corollary studies with reference sera from human vaccinees immunized with rPA or anthrax vaccine absorbed and nonhuman primates immunized with PA revealed no detectable Ab with specificity for the LND. We conclude that a synthetic peptide vaccine targeting the LND would be a potentially efficacious vaccine for anthrax.
Defective antibody-dependent tumour cell lysis by neutrophils from cancer patients. (1989)

Neutrophil antibody-dependent cellular cytotoxicity (ADCC) against Raji target cells was studied in 32 patients with lung or gastro-intestinal carcinoma and 25 healthy controls. Seventeen of the patients (53%) had defective ADCC. Moreover, neutrophils obtained from patients with defective ADCC were found to bind IgG-coated target cells normally. Thus, the defect responsible for the impaired lysis appears to be distal to the Fc receptor (FcR)-mediated target cell binding by neutrophils.
Exploiting Structural and Temporal Evolution in Dynamic Link Prediction (2018)

Link prediction in dynamic networks is an important task with many real-life applications in different domains, such as social networks, cyber-physical systems, and bioinformatics. There are two key processes in dynamic networks: network structural evolution and network temporal evolution, where the former represents interdependency between entities and their neighbors in the network at each timestamp, while the latter captures the evolving behavior of the entire network from the current timestamp to the next. Structural evolution generally assumes that a node is more likely to co-evolve with its neighbors in the near future. Temporal evolution focuses on the trend of network evolution as a whole, based on the accumulation of historical data. It is thus essential to use characteristics of both structural and temporal evolutions to emulate complex behaviors of dynamic networks. However, very few existing work considered both processes. In addition, real-life networks are often very sparse with limited observed links. A missing link between two nodes does not always imply that the two nodes do not have a relation in reality, especially when they share many common neighbors. Most existing methods only focus on the first-order proximity of networks, which is usually insufficient to capture the relationships among nodes.
Submicrometer periodicity gratings as artificial anisotropic dielectrics (1983)

Gratings of dielectric material can act as homogeneous birefringent materials if the wavelength of the incident radiation is greater than twice the period of the grating. For the case of square profile gratings, simple equations predict the birefringence versus linewidth-to-period ratio of the gratings. By using x-ray lithography and reactive ion etching, 240-nm period gratings of polymethylmethacrylate and silicon nitride were fabricated with various linewidths. The birefringence of these was measured at 632.8 nm and found to agree closely with the theory. Silicon nitride gratings which act as half-wave and quarter-wave plates in the visible were made.
Role of Renin-Angiotensin System and Nuclear Factor-κB in the Obstructed Kidney of Rats With Unilateral Ureteral Obstruction (2002)

The present study was conducted to elucidate the role of oxidative stress and nuclear factor-kappaB (NF-kappaB) in the beneficial effects of angiotensin receptor blockade on obstructive nephropathy. Unilateral ureteral occlusion in rats elicited tubulo-interstitial fibrosis with concomitant macrophage infiltration and increased expression of monocyte chemoattractant protein-1. These changes were accompanied by an induction of renal cortical lipid peroxidation and activation of NF-kappaB. Both an AT(1) antagonist, candesartan, and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated these changes and to a similar extent. These results suggest that the beneficial effects of angiotensin blockade are mediated by the inhibition of oxidative stress and subsequent NF-kappaB activation in obstructive nephropathy.
Multiplex sequencing of paired-end ditags (MS-PET): a strategy for the ultra-high-throughput analysis of transcriptomes and genomes (2006)

The paired-end ditagging (PET) technique has been shown to be efficient and accurate for large-scale transcriptome and genome analysis. However, as with other DNA tag-based sequencing strategies, it is constrained by the current efficiency of Sanger technology. A recently developed multiplex sequencing method (454-sequencing) using picolitre-scale reactions has achieved a remarkable advance in efficiency, but suffers from short-read lengths, and a lack of paired-end information. To further enhance the efficiency of PET analysis and at the same time overcome the drawbacks of the new sequencing method, we coupled multiplex sequencing with paired-end ditagging (MS-PET) using modified PET procedures to simultaneously sequence 200,000 to 300,000 dimerized PET (diPET) templates, with an output of nearly half-a-million PET sequences in a single 4 h machine run. We demonstrate the utility and robustness of MS-PET by analyzing the transcriptome of human breast carcinoma cells, and by mapping p53 binding sites in the genome of human colorectal carcinoma cells. This combined sequencing strategy achieved an approximate 100-fold efficiency increase over the current standard for PET analysis, and furthermore enables the short-read-length multiplex sequencing procedure to acquire paired-end information from large DNA fragments.
Cloning the shared components of complex DNA resources (1994)

The complex and repetitive nature of mammalian genomes limits the ability of conventional molecular techniques to recover sequences of interest. Here we describe a rapid and simple procedure for the direct cloning of sequences which are coincident between DNA mixtures of whole genome complexity. The system, called end ligation coincident sequence cloning (EL-CSC), can enrich coincident DNA by greater than 10(6)-fold and overcomes problems associated with repetitive elements. Applying EL-CSC to various paired DNA resources enables the facile cloning of both genomic markers and novel genes. To demonstrate the power of the method we have i) selectively purified single copy sequences from a complete genome, and ii) isolated gene fragments from 260 kb of cloned genomic DNA.
Pyrimidine Acyclic Nucleoside Phosphonates and Phosphorylated Analogs (Part 2): Syntheses and Investigation of Their Inhibitory Effects Towards Human Thymidine Phosphorylase (2008)

Various methods were used in the syntheses of a number of pyrimidine acyclic nucleoside phosphonates and their derivatives such as a nucleophilic fluorination, Suzuki-Miyaura coupling reactions and phosphorylation. These new compounds were further investigated for their potential biological activity. Based on results obtained the ability to inhibit human thymidine phosphorylase some of them was found.
Recognition and Cleavage of DNA by Type‐II Restriction Endonucleases (1997)

Restriction endonucleases are enzymes which recognize short DNA sequences and cleave the DNA in both strands. Depending on the enzymological properties different types are distinguished. Type II restriction endonucleases are homodimers which recognize short palindromic sequences 4-8 bp in length and, in the presence of Mg2+, cleave the DNA within or next to the recognition site. They are capable of non-specific binding to DNA and make use of linear diffusion to locate their target site. Binding and recognition of the specific site involves contacts to the bases of the recognition sequence and the phosphodiester backbone over approximately 10-12 bp. In general, recognition is highly redundant which explains the extreme specificity of these enzymes. Specific binding is accompanied by conformational changes over both the protein and the DNA. This mutual induced fit leads to the activation of the catalytic centers. The precise mechanism of cleavage has not yet been established for any restriction endonuclease. Currently two models are discussed: the substrate-assisted catalysis mechanism and the two-metal-ion mechanism. Structural similarities identified between EcoRI, EcoRV, BamHI, PvuII and Cfr10I suggest that many type II restriction endonucleases are not only functionally but also evolutionarily related.
Plasma Complement Components and Activation Fragments: Associations with Age-Related Macular Degeneration Genotypes and Phenotypes (2009)

Increased levels of activation fragments Bb and C5a are independently associated with AMD. Higher BMI is related to increased levels of complement components. C5a is associated with AMD genotypes. C statistics are stronger with the addition of C3a, Bb, and C5a in predictive models. Results implicate ongoing activation of the alternative complement pathway in AMD pathogenesis.
Endothelial cell injury by high glucose and heparanase is prevented by insulin, heparin and basic fibroblast growth factor (2005)

Endothelial cells injured by high glucose or heparinase I are protected by a combination of insulin, heparin and bFGF, although protection by heparin and/or bFGF was variable.
Role of Extracellular Phospholipases and Mononuclear Phagocytes in Dissemination of Cryptococcosis in a Murine Model (2004)

Secreted phospholipase B (PLB) activity promotes the survival and replication of Cryptococcus neoformans in macrophages in vitro. We therefore investigated the role of mononuclear phagocytes and cryptococcal PLB in the dissemination of infection in a mouse model, using C. neoformans var. grubii wild-type strain H99, a PLB1 deletion mutant (Delta plb1), and a reconstituted strain (Delta plb1(rec)). PLB facilitated the entry of endotracheally administered cryptococci into lung IM. PLB was also required for lymphatic spread from the lung to regional lymph nodes and for entry into the blood. Langhans-type giant cells containing budding cryptococci were seen free in the lymphatic sinuses of hilar nodes of H99- and Delta plb1(rec)-infected mice, suggesting that they may have a role in the dissemination of cryptococcal infection. The transfer of infected lung macrophages to recipient mice by tail vein injections demonstrated that these cells can facilitate hematogenous dissemination of cryptococci to the brain, independent of cryptococcal PLB secretion. PLB activities of cryptococci isolated from lung macrophages or infected brains were not persistently increased. We conclude that mononuclear phagocytes are a vehicle for cryptococcal dissemination and that PLB activity is necessary for the initiation of interstitial pulmonary infections and for dissemination from the lung via the lymphatics and blood. PLB is not, however, essential for the establishment of neurological infections when cryptococci are presented within, or after passage through, mononuclear phagocytes.
Monocyte Telomere Shortening and Oxidative DNA Damage in Type 2 Diabetes (2006)

Monocyte telomere shortening in type 2 diabetes could be due to increased oxidative DNA damage to monocyte precursors during cell division. This data suggests that monocytes adhering to vascular endothelium and entering the vessel wall in type 2 diabetes are from a population with shorter telomeres and at increased risk of replicative senescence within vascular plaque.
Designing Paclitaxel Drug Delivery Systems Aimed at Improved Patient Outcomes: Current Status and Challenges (2012)

Paclitaxel is one of the most widely used and effective antineoplastic agents derived from natural sources. It has a wide spectrum of antitumor activity, particularly against ovarian cancer, breast cancer, nonsmall cell lung cancer, head and neck tumors, Kaposi's sarcoma, and urologic malignancies. It is a highly lipophilic compound with a log P value of 3.96 and very poor aqueous solubility of less than 0.01 mg/mL. In addition, the compound lacks functional groups that are ionizable which could potentially lead to an increase in its solubility with the alteration in pH. Therefore, the delivery of paclitaxel is associated with substantial challenges. Until the introduction of Abraxane, only commercial formulation was solution of paclitaxel in cremophor, which caused severe side effects. However, in recent years, a number of approaches have been reported to solubilize paclitaxel using cosolvents and inclusion complexes. In addition, innovative approaches have been reported for passive targeting of tumors using nanoparticles, nanosuspensions, liposomes, emulsions, micelles, implants, pastes and gels. All approaches for delivery of improved therapeutic outcome have been discussed in this paper.
Hsp72-mediated augmentation of MHC class I surface expression and endogenous antigen presentation (1998)

Efficient recognition of tumor cells by cytolytic T lymphocytes (CTL) is often dependent on the presentation of cytosolic peptides in the context of MHC class I molecules. This process may be influenced by various molecular chaperones. To analyze this influence, we have utilized B16 melanoma cells, which are not effectively recognized by MHC class I-restricted CTL. This resistance to CTL is apparently due to a very low level of surface MHC expression. We have found that stably transfected clones of B16 which constitutively express the human heat shock protein 72 (Hsp72) exhibit significantly increased levels of MHC class I antigens on their surface. This Hsp72-mediated up-regulation of surface MHC class I antigen represents an increase in the amount of functional MHC-peptide complexes as measured by conformation-dependent antibodies and recognition by MHC class I-restricted CTL. Expression of Hsp72 did not improve the antigen presentation defect in cells lacking the activity of the transporter associated with antigen presentation (TAP). Moreover, mice immunized with Hsp72-expressing B16 cells, but not with control-transfected B16 cells, display significantly increased resistance to a subsequent challenge with live, wild-type B16. Together, our data demonstrate that the immune recognition of tumor cells can be substantially enhanced by the suitable expression of a molecular chaperone.
The Effects of Supraphysiologic Doses of Testosterone on Muscle Size and Strength in Normal Men (1996)

Supraphysiologic doses of testosterone, especially when combined with strength training, increase fat-free mass and muscle size and strength in normal men.