gebhart/patrepeval huggingface dataset:
Polyelectrolyte Vectors for Gene Delivery:  Influence of Cationic Polymer on Biophysical Properties of Complexes Formed with DNA (1999)

Cationic polymer/DNA complexes are widely used for gene delivery, although the influence of the cationic polymer on the biophysical properties of the resulting complex is poorly understood. Here, several series of cationic polymers have been used to evaluate the influence of structural parameters on properties of DNA complexes. Parameters studied included the length of side chain, charge type (primary versus tertiary and quaternary), polymer molecular weight, and charge spacing along the polymer backbone. Cationic polymers with short side chains (such as polyvinylamine) formed small complexes, resistant to destabilization by polyanions, with low surface charge, limited transfection activity, and efficient intranuclear transcription. Conversely, cationic polymers with long side chains (e.g., poly[methacryloyl-Gly-Gly-NH-(CH(2))(6)-NH(2))] showed inefficient complex formation, high positive surface charge, and better transfection activity. The effects of molecular weight varied between polymers, for example, low molecular weight poly(L-lysine) produced relatively small complexes, whereas low molecular weight poly[2-(trimethylammonio)ethyl methacrylate chloride] produced large aggregates. Polymers containing quaternary ammonium groups showed efficient complex formation but poor transfection. Finally, spreading charges widely on the polymer structure inhibited their ability to condense DNA. In summary, to achieve small, stable complexes, the use of cationic polymers with short side chains bearing primary amino groups is suggested.
Costimulation by B7-1 and B7-2 Is Required for Autoimmune Disease in MRL- Fas lpr Mice (2000)

Autoimmune lupus nephritis is dependent on infiltrating autoreactive leukocytes and Igs. B7 costimulatory molecules (B7-1 and B7-2) provide signals essential for T cell activation and Ig class switching. In MRL-Faslpr mice, a model of human lupus, although multiple tissues are targeted for autoimmune injury, nephritis is fatal. We identified intrarenal B7-1 and B7-2 expression, restricted to kidney-infiltrating leukocytes, before and increasing with progressive nephritis in MRL-Faslpr mice. Thus, we hypothesized that the B7 pathway is required for autoimmune disease in MRL-Faslpr mice. To investigate the role of B7 costimulatory molecules in this autoimmune disease, we generated a MRL-Faslpr strain deficient in B7-1 and B7-2. Strikingly, MRL-Faslpr mice lacking both B7 costimulators do not develop kidney (glomerular, tubular, interstitial, vascular) pathology, or proteinuria, and survive far longer. Intrarenal downstream effector transcripts (IFN-gamma, IL-12, monocyte chemoattractant protein-1, CSF-1) linked to nephritis remained at normal levels compared with wild-type mice. Skin lesions and lymphoid enlargement characteristic of MRL-Faslpr mice were diminished in B7-1/B7-2-deficient MRL-Faslpr mice. B7-1/B7-2-deficient MRL-Faslpr mice did not develop leukocytic infiltrates, elevated serum IgG and isotypes (G1,G2b,G3), autoantibodies, and intrarenal IgG deposits. Our findings demonstrate that B7-1 and B7-2 costimulatory pathways are critical to the pathogenesis of autoimmune lupus.
Predictors of survival following in-hospital adult cardiopulmonary resuscitation. (2002)

Overall, survival following cardiopulmonary resuscitation in hospital does not appear to have changed markedly in 40 years. The type of arrest is highly predictive of survival, whereas age and sex are not.
Nucleic acid detection with CRISPR-Cas13a/C2c2 (2017)

Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting clustered regularly interspaced short palindromic repeats (CRISPR) effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of promiscuous ribonuclease activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity. We use this Cas13a-based molecular detection platform, termed Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK), to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype human DNA, and identify mutations in cell-free tumor DNA. Furthermore, SHERLOCK reaction reagents can be lyophilized for cold-chain independence and long-term storage and be readily reconstituted on paper for field applications.
Purification of acyloxyacyl hydrolase, a leukocyte enzyme that removes secondary acyl chains from bacterial lipopolysaccharides (1989)

Leukocytes contain an enzyme that detoxifies bacterial lipopolysaccharides (also called endotoxins) by removing fatty acyl chains that are attached in acyloxy acyl linkage to the glucosamine backbone of lipid A. We describe the purification of an enzyme that carries out this activity, termed acyloxyacyl hydrolysis, from the HL-60 human promyelocyte cell line. The enzyme is a glycoprotein of apparent Mr = 52,000-60,000 that is found in low abundance (less than 0.001% of the cell lysate protein), principally in the granule fraction of the cells. The protein has two disulfide-linked subunits of apparent Mr = 50,000 and 14,000-20,000, each of which contains N-linked oligosaccharides. This is the first lipopolysaccharide-degrading enzyme that has been purified from animal cells.
Synthesis of human parathyroid‐hormone‐related protein(1–141) in Saccharomyces cerevisiae (1993)

Gene fusions have been widely used in heterologous expression systems as a technique to stabilize the recombinant product against proteolysis, increase the translational initiation efficiency or to serve as an affinity handle for the purification of the protein. A further advantage is the potential to generate an authentic amino terminus of the foreign protein when this is vital for its biological activity, such as for the ability of human parathyroid-hormone-related protein (hPTHrP) to mediate activation of adenylate cyclase. We report here the construction and utility of a ubiquitin fusion protein system for production of the otherwise short-lived hPTHrP(1-141) as a carboxyl extension to ubiquitin in yeast. A hybrid gene containing the hPTHrP(1-141) cDNA coding region fused in-frame to the 3' end of the yeast ubiquitin cDNA was constructed and expressed under the control of the regulatable yeast metallothionein promoter. The recombinant protein was purified to homogeneity and finally characterized by N-terminal amino acid sequencing and amino acid composition analysis, demonstrating that the fusion protein was cleaved correctly and quantitatively in vivo by an ubiquitin-specific yeast endoprotease to generate authentic hPTHrP(1-141). hPTHrP(1-141) stimulated adenylate cyclase in rat osteosarcoma cell membranes to the same extent as equimolar amounts of recombinant human parathyroid hormone(1-84) and [Tyr34]hPTHrP(1-34)amide. Thus, this expression cloning strategy permits the production of authentic, biologically active recombinant hPTHrP(1-141), and the procedure can easily be adapted to make PTHrP analogues for further studies of its domain-specific activities and biological roles.
Understanding Surface Adhesion in Nature: A Peeling Model (2016)

Nature often exhibits various interesting and unique adhesive surfaces. The attempt to understand the natural adhesion phenomena can continuously guide the design of artificial adhesive surfaces by proposing simplified models of surface adhesion. Among those models, a peeling model can often effectively reflect the adhesive property between two surfaces during their attachment and detachment processes. In the context, this review summarizes the recent advances about the peeling model in understanding unique adhesive properties on natural and artificial surfaces. It mainly includes four parts: a brief introduction to natural surface adhesion, the theoretical basis and progress of the peeling model, application of the peeling model, and finally, conclusions. It is believed that this review is helpful to various fields, such as surface engineering, biomedicine, microelectronics, and so on.
Secretin: structure of the precursor and tissue distribution of the mRNA. (1990)

Secretin is a 27-amino acid gastrointestinal hormone that stimulates the secretion of bicarbonate-rich pancreatic fluid. The unusually high number of serine, leucine, and arginine residues in secretin has precluded the use of oligonucleotides to screen cDNA libraries to isolate a secretin cDNA. In the present study, a short cDNA encoding porcine secretin was amplified from duodenal mucosal first-strand cDNA template by using 16,384- and 4096-fold degenerate primers in the DNA polymerase chain reaction. From the sequence of the amplified cDNA, an unambiguous oligonucleotide probe was designed to screen a cDNA library. Here we report the sequences of cDNAs encoding the porcine and rat secretin precursors. The predicted amino acid sequences reveal that each precursor consists of a signal peptide, an N-terminal peptide, secretin, and a 72-amino acid C-terminal peptide. Secretin has been highly conserved through evolution. Rat secretin differs from its porcine counterpart by a single glutamine-for-arginine substitution at position 14. In contrast, the amino acid sequences of the C-terminal peptides are only 39% conserved between the two species, suggesting that the C-terminal peptide does not have an essential physiologic function. RNA blot hybridizations reveal that the rat secretin gene is expressed throughout the small intestine. Although secretin immunoreactivity has been localized in the central nervous system by some laboratories, we are unable to detect secretin mRNA in tissues of the central nervous system by Northern blot hybridization.
Asirra: A captcha that exploits interest-aligned manual image categorization (2007)

We present Asirra (Figure 1), a CAPTCHA that asks users to iden-tify cats out of a set of 12 photographs of both cats and dogs. Asirra is easy for users; user studies indicate it can be solved by humans 99.6 % of the time in under 30 seconds. Barring a major advance in machine vision, we expect computers will have no better than a 1/54,000 chance of solving it. Asirra’s image database is provided by a novel, mutually beneficial partnership with Petfinder.com. In exchange for the use of their three million images, we display an “adopt me ” link beneath each one, promoting Petfinder’s primary mission of finding homes for homeless animals. We describe the design of Asirra, discuss threats to its security, and report early de-ployment experiences. We also describe two novel algorithms for amplifying the skill gap between humans and computers that can be used on many existing CAPTCHAs.
GlycoSuiteDB: a new curated relational database of glycoprotein glycan structures and their biological sources (2001)

GlycoSuiteDB is a relational database that curates information from the scientific literature on glyco-protein derived glycan structures, their biological sources, the references in which the glycan was described and the methods used to determine the glycan structure. To date, the database includes most published O:-linked oligosaccharides from the last 50 years and most N:-linked oligosaccharides that were published in the 1990s. For each structure, information is available concerning the glycan type, linkage and anomeric configuration, mass and composition. Detailed information is also provided on native and recombinant sources, including tissue and/or cell type, cell line, strain and disease state. Where known, the proteins to which the glycan structures are attached are reported, and cross-references to the SWISS-PROT/TrEMBL protein sequence databases are given if applicable. The GlycoSuiteDB annotations include literature references which are linked to PubMed, and detailed information on the methods used to determine each glycan structure are noted to help the user assess the quality of the structural assignment. GlycoSuiteDB has a user-friendly web interface which allows the researcher to query the database using mono-isotopic or average mass, monosaccharide composition, glycosylation linkages (e.g. N:- or O:-linked), reducing terminal sugar, attached protein, taxonomy, tissue or cell type and GlycoSuiteDB accession number. Advanced queries using combinations of these parameters are also possible. GlycoSuiteDB can be accessed on the web at http://www.glycosuite.com.
Transthyretin sequesters amyloid beta protein and prevents amyloid formation. (1994)

The cardinal pathological features of Alzheimer disease are depositions of aggregated amyloid beta protein (A beta) in the brain and cerebrovasculature. However, the A beta is found in a soluble form in cerebrospinal fluid in healthy individuals and patients with Alzheimer disease. We postulate that sequestration of A beta precludes amyloid formation. Failure to sequester A beta in Alzheimer disease may result in amyloidosis. When we added A beta to cerebrospinal fluid of patients and controls it was rapidly sequestered into stable complexes with transthyretin. Complexes with apolipoprotein E, which has been shown to bind A beta in vitro, were not observed in cerebrospinal fluid. Additional in vitro studies showed that both purified transthyretin and apolipoprotein E prevent amyloid formation.
Peripheral Electrical and Magnetic Stimulation to Augment Resistance Training (2016)

Electrical stimulation (ES) and magnetic stimulation (MS), applied peripherally, may be used to elicit muscle contractions to increase muscle hypertrophy, increase muscle strength and reduce knee laxity in rehabilitation following injury. We aimed to examine the effect of a three-week exercise programme designed to induce muscle hypertrophy augmented by peripheral ES and MS. We hypothesised that the use of peripheral stimulation to augment voluntary drive during a resistance-training protocol would induce more repetitions thus leading to increased thigh circumference, muscle layer thickness, and quadriceps strength whilst decreasing knee laxity. Thirty healthy participants were divided randomly into either ES, MS or Control groups. Five resistance training sessions were carried out, consisting of four sets of quadriceps extensions. During the first three sets the participants performed eight repetitions at 85% of their 1-repetition maximum (1-RM). On the last set, the participants were instructed to perform the exercise until failure. The augmentation of peripheral stimuli allowed the MS and ES groups to continue to exercise producing, on average, 4 ± 2 and 7 ± 6 additional repetitions with ES and MS, respectively. Following the training, significant increases were observed for both 1-RM (p = 0.005) and muscle layer thickness (p = 0.031) whilst no change was observed in thigh circumference (p = 0.365). Knee laxity decreased (p = 0.005). However, there were no significant differences in the stimulation groups compared with control for any of these measurements. The additional repetitions elicited by stimulation after the point of failure suggests that peripheral electrical and/or magnetic stimulation may be useful as an adjunct for resistance training. However, this effect of resistance training augmented by peripheral stimulation on hypertrophy, strength and knee laxity may be small.
Discrete Mathematical Structures With Applications To Computer Science (1975)

Discrete mathematical structures with applications to computer science , Discrete mathematical structures with applications to computer science , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
A detailed study of time‐dependent changes in human red blood cells: from reticulocyte maturation to erythrocyte senescence (2006)

The use of microfabrication technology in the study of biological systems continues to grow rapidly in both prevalence and ascendancy. Customised microdevices that provide superior results than traditional macroscopic methods can be designed in order to investigate specific cell types and cellular processes. This study showed the benefit of this approach in precisely characterising the progressive losses of surface area and haemoglobin (Hb) content by the human red blood cell (RBC), from newborn reticulocyte to senescent erythrocyte. The high-throughput, multiparametric measurements made on individual cells with a specialised microdevice enabled, for the first time, delineation and quantification of the losses that occur during the two stages of the human RBC lifespan. Data acquired on tens of thousands of red cells showed that nearly as much membrane area is lost during the 1-2 d of reticulocyte maturation (c. 10-14%) as in the subsequent 4 months of erythrocyte ageing (c. 16-17%). The total decrease in Hb over the red cell lifespan is also estimated (c. 15%) and a model describing the complete time-course of diminishing mean RBC area and Hb is proposed. The relationship between the losses of Hb and area, and their possible influence on red cell lifespan, are discussed.
Inactivation of the Mouse Huntington's Disease Gene Homolog Hdh (1995)

Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function. To distinguish between "loss of function" and "gain of function" models of HD, the murine HD homolog Hdh was inactivated by gene targeting. Mice heterozygous for Hdh inactivation were phenotypically normal, whereas homozygosity resulted in embryonic death. Homozygotes displayed abnormal gastrulation at embryonic day 7.5 and were resorbing by day 8.5. Thus, huntingtin is critical early in embryonic development, before the emergence of the nervous system. That Hdh inactivation does not mimic adult HD neuropathology suggests that the human disease involves a gain of function.
AbDesign: An algorithm for combinatorial backbone design guided by natural conformations and sequences (2015)

Computational design of protein function has made substantial progress, generating new enzymes, binders, inhibitors, and nanomaterials not previously seen in nature. However, the ability to design new protein backbones for function--essential to exert control over all polypeptide degrees of freedom--remains a critical challenge. Most previous attempts to design new backbones computed the mainchain from scratch. Here, instead, we describe a combinatorial backbone and sequence optimization algorithm called AbDesign, which leverages the large number of sequences and experimentally determined molecular structures of antibodies to construct new antibody models, dock them against target surfaces and optimize their sequence and backbone conformation for high stability and binding affinity. We used the algorithm to produce antibody designs that target the same molecular surfaces as nine natural, high-affinity antibodies; in five cases interface sequence identity is above 30%, and in four of those the backbone conformation at the core of the antibody binding surface is within 1 Å root-mean square deviation from the natural antibodies. Designs recapitulate polar interaction networks observed in natural complexes, and amino acid sidechain rigidity at the designed binding surface, which is likely important for affinity and specificity, is high compared to previous design studies. In designed anti-lysozyme antibodies, complementarity-determining regions (CDRs) at the periphery of the interface, such as L1 and H2, show greater backbone conformation diversity than the CDRs at the core of the interface, and increase the binding surface area compared to the natural antibody, potentially enhancing affinity and specificity.
Associative Properties in Water of Copolymers of Sodium 2-(Acrylamido)-2-methylpropanesulfonate and Methacrylamides Substituted with Alkyl Groups of Varying Lengths (2000)

Associative properties of random copolymers of sodium 2-(acrylamido)-2-methylpropanesulfonate (AMPS) with N-hexylmethacrylamide (C6MAm) and with N-octadecylmethacrylamide (C18MAm) in aqueous solutions were investigated comparing with those of AMPS copolymers with N-dodecylmethacrylamide (C12MAm) reported previously. For characterization by fluorescence, all the polymers were labeled with 1 mol % of naphthalene by terpolymerization using N-(1-naphthylmethyl)methacrylamide. The polymers possessing C6 or C12 alkyl chains exhibit a strong tendency for intramolecular hydrophobic association to form unimolecular micelles when the CnMAm (n = 6, 12) contents in the polymers are in the ranges of 30−70 and 10−50 mol % for the C6 and C12 chains, respectively. A similar tendency was observed for the polymers possessing C18 chains when the C18MAm contents are in the range of 5−20 mol %, but polymer micelles formed were not completely unimolecular. Both the lower and upper limits of the CnMAm contents for all the three polymers decrease significantly with increasing the length of the alkyl chain. When the CnMAm contents are either lower or higher than these limits, the polymer-bound alkyl chains undergo interpolymer associations. Fluorescence depolarization and 1H NMR relaxation times indicate that local motions of naphthalene labels and alkyl chains are more pronouncedly restricted in hydrophobic domains formed by longer alkyl chains. An inclination to the self-association of these polymers was discussed in terms of the ratio of the total number of carbon atoms in hydrophobes to the number of SO3- in a polymer chain. A conclusion is that with C6 chains one needs to incorporate more carbon atoms into a polymer than with C12 and C18 chains to attain the same extent of hydrophobe associations. In other words, the CH2 and CH3 residues in the C6 chain are much less effective than those in the C12 and C18 chains for the self-association when compared at the same hydrophobe/charge ratio in a polymer chain, whereas there is no significant difference between those in the C12 and C18 chains. Thus, the ability of the C6, C12, and C18 chains per carbon atom to associate is in the order C18 ≥ C12 ≫ C6.