gebhart/patrepeval huggingface dataset:
Liquid-infused structured surfaces with exceptional anti-biofouling performance (2012)

Bacteria primarily exist in robust, surface-associated communities known as biofilms, ubiquitous in both natural and anthropogenic environments. Mature biofilms resist a wide range of antimicrobial treatments and pose persistent pathogenic threats. Treatment of adherent biofilm is difficult, costly, and, in medical systems such as catheters or implants, frequently impossible. At the same time, strategies for biofilm prevention based on surface chemistry treatments or surface microstructure have been found to only transiently affect initial attachment. Here we report that Slippery Liquid-Infused Porous Surfaces (SLIPS) prevent 99.6% of Pseudomonas aeruginosa biofilm attachment over a 7-d period, as well as Staphylococcus aureus (97.2%) and Escherichia coli (96%), under both static and physiologically realistic flow conditions. In contrast, both polytetrafluoroethylene and a range of nanostructured superhydrophobic surfaces accumulate biofilm within hours. SLIPS show approximately 35 times the reduction of attached biofilm versus best case scenario, state-of-the-art PEGylated surface, and over a far longer timeframe. We screen for and exclude as a factor cytotoxicity of the SLIPS liquid, a fluorinated oil immobilized on a structured substrate. The inability of biofilm to firmly attach to the surface and its effective removal under mild flow conditions (about 1 cm/s) are a result of the unique, nonadhesive, "slippery" character of the smooth liquid interface, which does not degrade over the experimental timeframe. We show that SLIPS-based antibiofilm surfaces are stable in submerged, extreme pH, salinity, and UV environments. They are low-cost, passive, simple to manufacture, and can be formed on arbitrary surfaces. We anticipate that our findings will enable a broad range of antibiofilm solutions in the clinical, industrial, and consumer spaces.
I. EVIDENCE THAT ELEVATED LEVELS OF TUMOR NECROSIS FACTOR-ALPHA PREDICT REJECTION FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION (1990)

Plasma levels of tumor necrosis factor-alpha were measured in 50 adult patients following orthotopic liver transplantation. The mean (+/- SEM) plasma concentration of TNF-alpha was significantly higher in patients experiencing a rejection episode (941 +/- 83 pg/ml) than in those with a stable clinical course (240 +/- 6 pg/ml; P = 0.0001). Peak levels of TNF-alpha were usually found at the time of clinically diagnosed rejection, although elevated levels were observed 1-2 days earlier. First-week peak TNF-alpha levels were significantly higher in patients who suffered graft loss (2146 +/- 788 pg/ml) than in those who were discharged from the hospital without clinical evidence of rejection (581 +/- 93 pg/ml; P = 0.004). TNF-alpha levels were not correlated with white blood cell count (r2 = 0.004), cyclosporine levels (0.01), serum creatinine (0.002), serum bilirubin (0.05), serum SGOT (0.03), or SGPT (0.05). TNF-alpha levels were not elevated in four cases of viral hepatitis occurring after transplantation. We conclude that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. First-week TNF-alpha levels are also useful predictors of long-term graft outcome. Further investigation is required to determine whether this monokine is important in the actual pathogenesis of allograft rejection.
Thrombotic mechanisms in atherosclerosis: potential impact of soy proteins. (1995)

Generally injuries that remove or disrupt the endothelial cells lining blood vessels stimulate formation of vascular lesions composed of smooth muscle cells. One of the first events after such endothelial cell disruption is the generation of thrombin at the site of injury. This leads to platelet activation and thrombus formation. Evidence suggests that thrombus formation may stimulate smooth muscle-cell proliferation through the action of any number of factors emanating from the thrombus including platelet- or macrophage-derived factors, platelet-derived growth factor, basic fibroblast growth factor or thrombin. Atherosclerotic plaques continue to grow for many years. The slow indolent process of nondenuding chemical injury of the endothelium and lesion formation may be accelerated periodically by thrombi forming on the lumenal surface at sites of small denuding injuries leading to progressive atherosclerotic disease. Genistein, an isoflavonoid derived from soy products, has been shown to inhibit thrombin formation and platelet activation in vitro in addition to its antigrowth factor activity. Should it have similar actions in vivo, this compound has the potential to affect the progression of atherosclerotic disease by modifying coagulation responses. To assess the potential of genistein as a therapeutic for vascular disease, additional studies will be required to establish its effect on experimental vascular lesion formation.
Interpretation of proper nouns for information retrieval (1993)

Most of the unknown words in texts which degrade the performance of natural language processing systems are proper nouns. On the other hand, proper nouns are recognized as a crucial source of information for identifying a topic in a text, extracting contents from a text, or detecting relevant documents in information retrieval (Rau, 1991).
Public-key cryptosystem design based on factoring and discrete logarithms (1994)

Most existing cryptosystem designs incorporate just one cryptographic assumption, such as factoring or discrete logarithms. These assumptions appear secure today; but, it is possible that efficient algorithms will be developed in the future to break one or more of these assumptions. It is very unlikely that multiple cryptographic assumptions would simultaneously become easy to solve. Enhancing security is the major objective for cryptosystems based on multiple assumptions. K.S. McCurley (1990) proposed the first key distribution system based on two dissimilar assumptions, both of which appear to be hard. In his design, the sizes of the security parameters for these two assumptions are quite different. The modulus to satisfy the proper security requirement for one assumption is too large for the other assumption. The side effects are (1) the public key size is larger than the original Diffie-Hellman key distribution scheme; and (2) more computation time is required. The authors propose a cryptographic system design based on the two popular assumptions: factoring and discrete logarithms. Breaking this system is computationally infeasible because it requires (1) solving the Diffie-Hellman discrete logarithm problem in a subgroup of Zp*, where p=2p&apos;*q&apos;+1 and p&apos;, q&apos; are two large primes, and (2) factoring (p-1)/2 into two large primes, p&apos; and q&apos;. Thus, in the proposed system it is possible to choose the same size of security parameter for these two assumptions and, therefore, to maintain the efficiency of the implementation.
Scattering by ionization and phonon emission in semiconductors. II. Monte Carlo calculations (1983)

Calculations of the pair-creation energy $\ensuremath{\epsilon}$ and the Fano factor $F$ for semiconductors are done for the assumptions that in each scattering event all possible sets of product particles are equally probable, that the energy bands are those of free particles separated by a band gap ${E}_{g}$, and that there is a single phonon energy $\ensuremath{\hbar}{\ensuremath{\omega}}_{0}$. The results from calculations done previously with the use of a recursive method are corroborated and expanded with the use of the Monte Carlo method. The electron-phonon interaction is divided into a deformation-potential interaction and a polar-mode electrostatic interaction, and the $\ensuremath{\hbar}{\ensuremath{\omega}}_{0}$ dependence of these interactions is incorporated into the calculations. New values of $\ensuremath{\epsilon}$ and $F$ are calculated. For many semiconductors, the accord of these values with experiments is as good as the accord of previous calculations done with the deformation potential alone, indicating the insensitivity of $\ensuremath{\epsilon}$ to the added interaction.
CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing (2014)

Major advances in genome editing have recently been made possible with the development of the TALEN and CRISPR/Cas9 methods. The speed and ease of implementing these technologies has led to an explosion of mutant and transgenic organisms. A rate-limiting step in efficiently applying TALEN and CRISPR/Cas9 methods is the selection and design of targeting constructs. We have developed an online tool, CHOPCHOP (https://chopchop.rc.fas.harvard.edu), to expedite the design process. CHOPCHOP accepts a wide range of inputs (gene identifiers, genomic regions or pasted sequences) and provides an array of advanced options for target selection. It uses efficient sequence alignment algorithms to minimize search times, and rigorously predicts off-target binding of single-guide RNAs (sgRNAs) and TALENs. Each query produces an interactive visualization of the gene with candidate target sites displayed at their genomic positions and color-coded according to quality scores. In addition, for each possible target site, restriction sites and primer candidates are visualized, facilitating a streamlined pipeline of mutant generation and validation. The ease-of-use and speed of CHOPCHOP make it a valuable tool for genome engineering.
Transfer RNA is required for conjugation of ubiquitin to selective substrates of the ubiquitin- and ATP-dependent proteolytic system. (1986)

Degradation of intracellular proteins via the ubiquitin- and ATP-dependent proteolytic pathway involves several steps. In the initial event, ubiquitin, an abundant 76-residue polypeptide is covalently linked to the protein substrate in an ATP-requiring reaction. Proteins marked by ubiquitin are selectively proteolyzed in a reaction that also requires ATP. Ubiquitin conjugation to proteins appears also to be involved in regulation of cell cycle and cell division, and probably in the regulation of gene expression at the level of chromatin structure. We have previously shown (Ciechanover, A., Wolin, S. L., Steitz, J. A., and Lodish, H. F. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 1341-1345) that transfer RNA is an essential component of the ubiquitin pathway. Ribonucleases strongly and specifically inhibited the degradation of 125I-labeled bovine serum albumin, while tRNA purified from reticulocyte extract could restore the proteolytic activity. Specifically, pure tRNAHis isolated by immunoprecipitation with human autoimmune serum could restore the proteolytic activity. Here we demonstrate that tRNA is required for conjugation of ubiquitin to some but not all proteolytic substrates of the ubiquitin mediated pathway. Conjugation of 125I-labeled ubiquitin to reduced carboxymethylated bovine serum albumin, alpha-lactalbumin, and soybean trypsin inhibitor was strongly and specifically inhibited by ribonucleases. Consequently, the ATP-dependent degradation of these substrates in the cell-free ubiquitin-dependent reticulocyte system was inhibited as well. Addition of tRNA to the ribonuclease inhibited system (following inhibition of the ribonuclease) restored both the conjugation activity and the ubiquitin- and ATP-dependent degradation of these substrates. Conjugation of ubiquitin to some endogenous reticulocyte proteins was also inhibited by ribonucleases and could be restored by the addition of tRNA. In striking contrast, the conjugation of radiolabeled ubiquitin to lysozyme, oxidized RNase A, alpha-casein, and beta-lactoglobulin was not affected by the ribonuclease treatment, and the degradation of these substrates was significantly accelerated by the ribonucleases. These findings indicate that there are at least two distinct ubiquitin conjugation systems. One requires tRNA, and the other is tRNA independent. These pathways, however, must share some common component(s) of the system, since the inhibition of one system accelerates the other. The possible function of tRNA in the selective conjugation reaction and the possible role of the two distinct ubiquitin marking mechanisms are discussed.
Cotinine Inhibits Amyloid-β Peptide Neurotoxicity and Oligomerization (2012)

Alzheimer’s disease, the main cause of dementia, correlates with an increase in the brain levels of aggregated forms of amyloid-β (Aβ) peptide. We investigated the effect of cotinine, the main metabolite of nicotine, on Aβ 1-42 neurotoxicity. Compared to nicotine, cotinine has a longer plasma half-life, lower toxicity and is a poor agonist of the nicotinic acetylcholine receptors (nAChRs). We found that cotinine promoted the survival of primary cortical neurons exposed to Aβ 1-42 . This neuroprotective effect was independent of the agonistic activation of the nAChRs and it was not prevented by the general nAChR antagonist mecamylamine. However, it was prevented by the pre-aggregation of Aβ in absence of cotinine, suggesting that inhibition of Aβ 1-42 aggregation by cotinine is a key mechanism mediating its neuroprotective activity. The analysis of Aβ 1-42 aggregation using dot blot immunoassay showed that cotinine inhibits its oligomerization. These results suggest that cotinine is neuroprotective at least in part by preventing the aggregation of the amyloid peptide. We previously found that cotinine prevented memory loss and reduced plaques in the brain of Tg6799 mice. This study suggests that cotinine can also inhibit neuronal cell death induced by Aβ neurotoxicity.
Automated selection of aptamers against protein targets translated in vitro: from gene to aptamer (2002)

Reagents for proteome research must of necessity be generated by high throughput methods. Aptamers are potentially useful as reagents to identify and quantitate individual proteins, yet are currently produced for the most part by manual selection procedures. We have developed automated selection methods, but must still individually purify protein targets. Therefore, we have attempted to select aptamers against protein targets generated by in vitro transcription and translation of individual genes. In order to specifically immobilize the protein targets for selection, they are also biotinylated in vitro. As a proof of this method, we have selected aptamers against translated human U1A, a component of the nuclear spliceosome. Selected sequences demonstrated exquisite mimicry of natural binding sequences and structures. These results not only reveal a potential path to the high throughput generation of aptamers, but also yield insights into the incredible specificity of the U1A protein for its natural RNA ligands.
STUDIES ON THE PROPERTIES OF SOIL‐BORNE VIRUSES OF THE TOBACCO‐RATTLE TYPE OCCURRING IN SCOTLAND (1959)

Soil‐borne viruses of the tobacco‐rattle type occur in sandy and peaty soils in many parts of Scotland, and infect many species of crop and weed plants, often only in the roots. They also occur in potato plants that have diseases of the stem‐mottle type. The viruses can be distinguished from other soil‐borne viruses occurring in Britain by the symptoms they cause in tobacco, Chenopodium amaranticolor and French bean. Some virus cultures (M types) multiplied readily and were easily transmitted by mechanical inoculation, whereas others (NM types) were transmitted mechanically only with difficulty. The behaviour of NM types remained constant during twenty successive subcultures. Only slight differences were noted between the symptoms caused by M and by NM types. A proportion of the single‐lesion isolates made from cultures of the M type behaved in every way like NM types: this proportion differed with different parent cultures. Single‐lesion isolates that were of the M type mostly caused somewhat different symptoms from their parent culture. All M types that were tested, including one from the Netherlands, were serologically related: however, different cultures, and different samples of the same culture propagated on different occasions, varied in antigenic constitution. Belladonna mosaic virus, described by Smith (1943) from England, was serologically related to tobacco rattle virus. Infection with each of several M types (including the Dutch culture), protected Nicotiana sylvestris plants from the effects of each of the others. NM types also protected N. sylvestris from the effects of the Dutch culture, but the latter was subsequently isolated from the tip leaves of such plants. Sap from plants infected with cultures of the M type contained characteristic rod‐shaped particles, but none was seen in sap from plants infected with NM types. In tobacco sap, M types had the following properties: thermal inactivation point, 80–85°C.; dilution end‐point, 10 ‐5 ‐10 ‐6 ; longevity in vitro , over 6 weeks; infectivity survived freezing and precipitation by ammonium sulphate, but not exposure to pH 3. In many of its properties, including the unusual one of failing to show photoreactivation after ultra‐violet irradiation, tobacco rattle virus resembles tobacco mosaic virus. Soil‐borne viruses occurring in Britain are classified into three groups, exemplified by tobacco necrosis, tomato black ring and tobacco rattle viruses.
Synthesis of Novel Nucleic Acid Mimics via the Stereoselective Intermolecular Radical Coupling of 3‘-Iodo Nucleosides and Formaldoximes1 (1996)

A highly convergent free radical coupling of alkyl iodides and oximes, mediated by bis(trimethylstannyl) benzopinacolate (8), has been utilized to prepare a series of dimeric nucleosides as mimics of natural nucleic acids. The systematic optimization of the reaction conditions allowed for the single-step conversion of the appropriate iodides and oximes into the 2'-deoxy dimers 9 in moderate to excellent yields. For example, the reaction of 3'-deoxy-3'-iodo-5'-(triphenylmethyl)thymidine (6a) with 3'-O-(tert-butyldiphenylsilyl)-5'-O-(methyleneimino)thymidine (7a) in the presence of 8 in degassed benzene gave an 81% yield of 3'-de(oxyphosphinico)-3'-(methyleneimino)-5'-O-(triphenylmethyl)thymidylyl-(3'-->5')-3'-O-(tert-butyldiphenylsilyl)thymidine (9a). Similarly prepared were dimers containing both pyrimidine (thymine, 5-methylcytosine) and purine (adenine, guanine) bases. The reaction was highly stereoselective, giving only a single dimeric species having the ribo-configuration of the newly introduced C-3'-branched methylene moiety. Also prepared were dimers 16, incorporating 2'-O-methyl ribonucleosides in both halves of the dimer. This required the synthesis of 3'-deoxy-3'-iodo-2'-O-methyl nucleosides 12 as well as 2'-O-methyl-5'-O-methyleneimino nucleosides 15. For example, 5'-O-(tert-butyldiphenylsilyl)-3'-deoxy-3'-iodo-2'-O-methyl-5-methyluridine (12e) was prepared in 80% yield by displacement of the corresponding triflate with Bu(4)NI. Also prepared were the suitably protected 3'-deoxy-3'-iodo adenosine and guanosine derivatives. Compounds 15 were prepared in high yield by a regioselective Mitsunobu reaction to give the corresponding 5'-O-phthalimido nucleosides 13, which were subsequently converted to the requisite oximes 15. In the 2'-O-methyl series, the pinacolate coupling reaction proceeded with efficiency equal to that observed for the 2'-deoxy series 9, but with slightly less stereoselectivity, giving predominantly the C-3'ribo products 16, contaminated with 5-25% of the epimeric material. Mixed base dimers containing both pyrimidine and purine bases at all possible positions, including purine-purine dimers were prepared. The hydroxylamine or methyleneimino (MI) backbone of several representative dimers so prepared was converted via methylation to give the corresponding methylenemethylimino (MMI)-linked compounds, which are novel phosphate surrogates for use in antisense oligonucleotides.
Evidence for mucins and sialic acid as receptors for Pseudomonas aeruginosa in the lower respiratory tract (1983)

The nature of the receptors for mucoid and nonmucoid Pseudomonas aeruginosa was investigated by using adherence to injured tracheal epithelium as a model. Bovine submaxillary mucin and crude rat tracheal mucin inhibited the adherence of both types of P. aeruginosa. Among the sugars present in these mucins only N-aceylneuraminic acid inhibited adherence. Inhibition of adherence probably involved the binding of N-acetylneuraminic acid to the bacterial cells and not to the tracheal cells. The mucoid strain appeared to be much more sensitive to inhibition by N-acetylneuraminic acid. Periodate oxidation and cholera filtrate also reduced the adherence of both strains, but Clostridium perfringens neuraminidase treatment did not alter adherence. A nonmucoid isogenic mutant of an unstable mucoid strain was also inhibited by N-acetylneuraminic acid. These data suggest that the receptor for P. aeruginosa is a sialic acid moiety on cell surfaces or in mucins.
Identification of a peptide fragment from the carboxyl-terminal extension region (E-domain) of rat proinsulin-like growth factor-II. (1985)

A fragment of the carboxyl-terminal extension region (E-peptide) of rat proinsulin-like growth factor-II has been purified from medium conditioned by cultured BRL-3A rat liver cells. The fragment, identified by microsequence analysis, was discovered in a biologically active fraction of insulin-like growth factor II (IGF-II). The fragment begins at position 117 in pro-IGF-II, two amino acids downstream from an Arg-Arg potential prohormone processing site. A synthetic analogue of the E-peptide at high concentrations stimulates [3H]thymidine incorporation in NIL8 hamster cells, raising the possibility that the E-peptide might bind with low affinity to a mitogen receptor. Peptides from the E-regions of pro-IGF-I and pro-IGF-II should be useful for development of radioimmunoassays for measurement of the somatic production of IGF-I and IGF-II, analogous to the radioimmunoassay for the insulin C-peptide.
Efficient Replication of Hepatitis C Virus Genotype 1a RNAs in Cell Culture (2003)

Hepatitis C virus (HCV) genotype 1 (subtypes 1a and 1b) is responsible for the majority of treatment-resistant liver disease worldwide. Thus far, efficient HCV RNA replication has been observed only for subgenomic and full-length RNAs derived from genotype 1b isolates. Here, we report the establishment of efficient RNA replication systems for genotype 1a strain H77. Replication of subgenomic and full-length H77 1a RNAs required the highly permissive Huh-7.5 hepatoma subline and adaptive amino acid substitutions in both NS3 and NS5A. Replication could be detected by RNA quantification, fluorescence-activated cell sorting, and metabolic labeling of HCV-specific proteins. Replication efficiencies were similar for subgenomic and full-length RNAs and were most efficient for HCV RNAs lacking heterologous RNA elements. Interestingly, both subtype 1a and 1b NS3 adaptive mutations are surface exposed and present on only one face of the NS3 structure. The cell culture-adapted subtype 1a replicons should be useful for basic replication studies and for antiviral development. These results are also encouraging for the development of adapted replicons for the remaining HCV genotypes.