gebhart/patrepeval huggingface dataset:
The evolution of methicillin resistance in Staphylococcus aureus : Similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones (2001)

The key genetic component of methicillin resistance, the mecA determinant, is not native to Staphylococcus aureus. Thus, the evolution of methicillin-resistant S. aureus (MRSA) must have begun with the acquisition of the mecA determinant from an unknown heterologous source some time before the first reported appearance of MRSA isolates in clinical specimens in the U.K. and Denmark (in the early 1960s). We compared the genetic backgrounds and phenotypes of a group of methicillin-susceptible S. aureus (MSSA) isolates to the properties of MRSA strains isolated in Denmark and the U.K. during the same time period, and also to the genetic profiles of contemporary epidemic clones of MRSA. All early MRSA isolates resembled a large group of the early MSSA blood isolates in phenotypic and genetic properties, including phage group, antibiotype (resistance to penicillin, streptomycin, and tetracycline), pulsed-field gel electrophoresis pattern, and spaA type and multilocus sequence type, strongly suggesting that the early MSSA examined here represented the progeny of a strain that served as one of the first S. aureus recipients of the methicillin-resistance determinant in Europe. The genetic background of this group of early MSSA isolates was also very similar to that of the widely disseminated contemporary "Iberian clone" of MRSA, suggesting that genetic determinants present in early MSSA and essential for some aspects of the epidemicity and/or virulence of these strains may have been retained by this highly successful contemporary MRSA lineage.
Analysis of effects of oxidized multiwalled carbon nanotubes on electro-optic polymer/liquid crystal thin film gratings (2010)

This work focuses on experimentally demonstrating the modification in diffusion kinetics, formation of holographic polymer dispersed liquid crystal gratings and an improvement in its electro optic response by doping them with multi-walled carbon nanotubes. Results indicate a faster rise and fall times which is attributed to the reduction in size of the liquid crystal droplets formed and a reduction in switching voltage due to change in dielectric properties of the medium as manifested by a rise in capacitance. Real time diffraction efficiency measurements reveal a time delay in the appearance of the diffracted order due to non-participation of the nanotube in the polymerization induced phase separation process. An analysis of this effect is presented based on the Stoke-Einstein's diffusion equation incorporating shape anisotropy of the nanotubes.
A texaphyrin–oxaliplatin conjugate that overcomes both pharmacologic and molecular mechanisms of cisplatin resistance in cancer cells (2012)

A texaphyrin-oxaliplatin conjugate, oxaliTEX, was designed to test the concept that a platinum analog can overcome defects in drug accumulation and p53-dependent DNA damage response in a tumor model expressing multifactorial mechanisms of cisplatin resistance. Cytotoxic studies resulted in a resistance factor of only 1.2, which essentially indicated complete reversal of resistance in 2780CP cells expressing a factor of 22 with cisplatin. Unlike cisplatin, oxaliTEX accumulated and formed DNA adducts, stabilized and activated p53 at similar levels in both sensitive and resistant cells, and induced apoptosis in both models. The ability and importance of a designer drug, such as oxaliTEX, to overcome cisplatin resistance by targeting two dominant resistance mechanisms is discussed.
Inhibition of a Class C β-Lactamase by a Specific Phosphonate Monoester (1989)

A phosphonate monoester, m-carboxyphenyl phenylacetamidomethylphosphonate, has been found to be a specific inhibitor of the class C beta-lactamase of Enterobacter cloacae P99. Inactivation is rapid (10(3) per second per molar concentration) and reactivation very slow (2.2 X 10(-6) per second). Apparently concerted with the inactivation, one equivalent (with respect to the enzyme) of m-hydroxybenzoate is released. Reactivation is accelerated by hydroxylamine and benzohydroxamate. This suggests that the loss of enzyme activity is due to phosphonylation of an active site functional group. This discovery holds the promise of a new general class of beta-lactamase inhibitors and, perhaps, antibiotics.
Recent Advances in the Application of N,O-Dialkylhydroxylamines in Organic Chemistry (2003)

N,O-Disubstituted hydroxylamines (R1NHOR2 or NODHA), unlike the O-monosubstituted derivatives, have received little attention so far. However, they have recently become important as intermediates for synthesizing complex nitrogen-containing compounds, especially natural products and their analogues. The formation of NODHA by stereoselective reduction, nucleophile and radical additions provides access to acyclic, carbo- and heterocyclic amines, many of which are naturally occurring and biologically active. New methods developed for the acylation of N,O-dimethylhydroxylamine and polymer-bound N,O-disubstituted hydroxylamines are an improvement on the Weinreb amide methodology and provide convenient routes to complex aldehydes and ketones as well as hydroxamic acids. Reductive and base-induced cleavage of the N-O bond of N,O-disubstituted hydroxylamines makes them valuable intermediates for preparing highly functionalized amines. Methods for the synthesis of bis(alkoxyamines) and their use as precursors to alkoxy-substituted heterocycles are described. Their bisnitroso derivatives on intramolecular cyclization provide an entry to hitherto unknown 4,5-dihydro-1,2,3-triazole 2-oxides. Finally, the review describes recent studies of naturally occurring and biologically active N,O-disubstituted hydroxylamines.
Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer (2004)

Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer.
Calculations of the barrier height and charge distribution of a metal–dielectric interface (1992)

We present calculations of the barrier height (work function) and charge distribution of a metal–dielectric interface using a self-consistent density functional method. The metal was modeled by a semiinfinite jellium and the dielectric was characterized by a single dielectric constant. Results show a monotonic decrease of over 2 eV in the work function of high density simple metals such as aluminum with increasing dielectric constant. As the dielectric constant becomes large, the work function approaches a constant value. This change is much larger than the roughly 0.5 eV change found by others using a variational density functional method, which also showed the work function increasing as the dielectric constant becomes large (ε≳10). Low electron density metals display a smaller decrease in work function as the dielectric constant increases, due to the smaller electrostatic dipole layer at the interface. As a consequence, the work function difference between high and low electron density simple metals narrows from 1.1 to 0.15 eV in the limit of infinite screening. Similar work function screening effects are expected for noble metals, although the difference in work functions between noble metals may not be reduced as much as simple metals. These results are discussed in relation to current Schottky barrier theories and are compared to other models of metal–semiconductor interfaces.
XVII. On a peculiar class of acoustical figures; and on certain forms assumed by groups of particles upon vibrating elastic surfaces (1831)

Abstract 1. The beautiful series of forms assumed by sand, filings, or other grains, when lying upon vibrating plates, discovered and developed by Chladni, are so striking as to be recalled to the minds of those who have seen them by the slightest reference. They indicate the quiescent parts of the plates, and visibly figure out what are called the nodal lines. 2. Afterwards M. Chladni observed that shavings from the hairs of the exciting violin bow did not proceed to the nodal lines, but were gathered together on those parts of the plate the most violently agitated, i. e. at the centres of oscillation. Thus when a square plate of glass held horizontally was nipped above and below at the centre, and made to vibrate by the application of a violin bow to the middle of one edge, so as to produce the lowest possible sound, sand sprinkled on the plate assumed the form of a diagonal cross; but the light shavings were gathered together at those parts towards the middle of the four portions where the vibrations were most powerful and the excursions of the plate greatest.
Potent and sustained cellular inhibition of miR-122 by lysine-derivatized peptide nucleic acids (PNA) and phosphorothioate locked nucleic acid (LNA)/2'-O-methyl (OMe) mixmer anti-miRs in the absence of transfection agents (2011)

Efficient cell delivery of antisense oligonucleotides (ONs) is a key issue for their potential therapeutic use. It has been shown recently that some ONs can be delivered into cells without the use of transfection agents (gymnosis), but this generally requires cell incubation over several days and high amounts of ONs (micromolar concentrations). Here we have targeted microRNA 122 (miR-122), a small non-coding RNA involved in regulation of lipid metabolism and in the replication of hepatitis C virus, with ONs of different chemistries (anti-miRs) by gymnotic delivery in cell culture. Using a sensitive dual-luciferase reporter assay, anti-miRs were screened for their ability to enter liver cells gymnotically and inhibit miR-122 activity. Efficient miR-122 inhibition was obtained with cationic PNAs and 2'-O-methyl (OMe) and Locked Nucleic Acids (LNA)/OMe mixmers containing either phosphodiester (PO) or phosphorothioate (PS) linkages at sub-micromolar concentrations when incubated with cells for just 4 hours. Furthermore, PNA and PS-containing anti-miRs were able to sustain miR-122 inhibitory effects for at least 4 days. LNA/OMe PS anti-miRs were the most potent anti-miR chemistry tested in this study, an ON chemistry that has been little exploited so far as anti-miR agents towards therapeutics.
AIDS and Malnutrition (1995)

The immune system is impaired by either malnutrition or human immunodeficiency virus infection. When these occur together, their compounding effects promote altered metabolism, inadequate intake, and malabsorption, which further impair immune function and contribute to human immunodeficiency virus wasting. Careful dietary management can help meet nutritional needs without further compromising the immune status of the person living with acquired immune deficiency syndrome.
A unified genetic, computational and experimental framework identifies functionally relevant residues of the homing endonuclease I-BmoI (2010)

Insight into protein structure and function is best obtained through a synthesis of experimental, structural and bioinformatic data. Here, we outline a framework that we call MUSE (mutual information, unigenic evolution and structure-guided elucidation), which facilitated the identification of previously unknown residues that are relevant for function of the GIY-YIG homing endonuclease I-BmoI. Our approach synthesizes three types of data: mutual information analyses that identify co-evolving residues within the GIY-YIG catalytic domain; a unigenic evolution strategy that identifies hyper- and hypo-mutable residues of I-BmoI; and interpretation of the unigenic and co-evolution data using a homology model. In particular, we identify novel positions within the GIY-YIG domain as functionally important. Proof-of-principle experiments implicate the non-conserved I71 as functionally relevant, with an I71N mutant accumulating a nicked cleavage intermediate. Moreover, many additional positions within the catalytic, linker and C-terminal domains of I-BmoI were implicated as important for function. Our results represent a platform on which to pursue future studies of I-BmoI and other GIY-YIG-containing proteins, and demonstrate that MUSE can successfully identify novel functionally critical residues that would be ignored in a traditional structure-function analysis within an extensively studied small domain of approximately 90 amino acids.
Si incorporation in laser-melted AlxGa1−xAs-GaAs quantum well heterostructures from a dielectric source (1990)

Data are presented describing the incorporation of Si in locally laser-melted AlxGa1−xAs-GaAs quantum well heterostructures from a thin-film dielectric source. The composition of the melted material, the effects of the Si source (SiO2 or Si3N4) on impurity incorporation, and the doping behavior are examined via secondary-ion mass spectroscopy, electron dispersion x-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. The data indicate that upon melting, a (Si)y(AlxGa1−xAs)1−y alloy is formed from which impurity-induced layer disordering may be effected. After annealing the melt region is found to contain crystalline segregates, which are attributed to rapid thermal quenching of the melt. Applications of these results to the fabrication of buried-heterostructure lasers by laser-assisted disordering are discussed.
Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments (2020)

High-frequency irreversible electroporation (H-FIRE) has emerged as an alternative to conventional irreversible electroporation (IRE) to overcome the issues associated with neuromuscular electrical stimulation that appear in IRE treatments. In H-FIRE, the monopolar pulses typically used in IRE are replaced with bursts of short bipolar pulses. Currently, very little is known regarding how the use of a different waveform affects the cell death dynamics and mechanisms. In this study, human pancreatic adenocarcinoma cells were treated with a typical IRE protocol and various H-FIRE schemes with the same energized time. Cell viability, membrane integrity and Caspase 3/7 activity were assessed at different times after the treatment. In both treatments, we identified two different death dynamics (immediate and delayed) and we quantified the electric field ranges that lead to each of them. While in the typical IRE protocol, the electric field range leading to a delayed cell death is very narrow, this range is wider in H-FIRE and can be increased by reducing the pulse length. Membrane integrity in cells suffering a delayed cell death shows a similar time evolution in all treatments, however, Caspase 3/7 expression was only observed in cells treated with H-FIRE.
Design of a trigeneration system using a high-temperature fuel cell (2009)

Fuel cells are one of the technologies available for combined heat, cooling and power production (CHCP) systems. They offer several advantages over more conventional systems, but they still need to overcome a number of barriers until they are readily available for commercialization. At this stage, it is important to fund demonstration projects that experiment with fuel cell technology in pre-commercial situations. In this context, a CHCP system, using a high-temperature fuel cell (solid oxide fuel cells, SOFC) and an absorption chiller, was designed in order to meet the energetic demands of a hospital for electricity, cooling, heating and hot water. The hospital load profile was determined taking into consideration the hourly energy consumption for four different typical days in the year. The CHCP system was designed so that the fuel cell meets the electrical demand of the hospital and, since the SOFC did not produce enough thermal energy, a boiler was considered. The artificial thermal efficiency of the CHCP system is 68%. The investment analysis is presented and it is concluded that, at the present and at three other scenarios, the system is not financially feasible. Despite this conclusion, it is important to invest on demonstration projects to help fuel cells reach commercialization. Copyright © 2008 John Wiley & Sons, Ltd.
Clinical-Scale Generation of Dendritic Cells in a Closed System (2003)

Immunotherapy of malignant diseases based on dendritic cells (DCs) pulsed with tumor antigens is a promising approach. Therefore, there is a demand for large-scale, clinical-grade ex vivo generation of DCs. Here, a procedure is presented that combines monocyte selection and tissue culture in closed systems under current good manufacturing practice conditions. Leukocytes from three patients with urologic cancers were collected by leukapheresis and subjected to immunomagnetic enrichment. From leukapheresis products containing 1.6 +/- 0.2 x 1010 (mean +/- SEM) leukocytes with a frequency of CD14+ monocytes of 18.7 +/- 2.3%, monocytes were enriched to 94.3 +/- 2.2%. CD14+ cell recovery was 67.0 +/- 4.7%. After 6 days of culture in Teflon bags in X-Vivo 15 medium supplemented with autologous plasma, GM-CSF, and IL-4, cells showed an immature DC phenotype and efficient antigen uptake. Following an additional 3 days of culture in the presence of GM-CSF, IL-4, IL-1beta, IL-6, TNFalpha, and PGE(2), cells (82.0 +/- 5.8% CD83+) displayed a mature DC morphology and phenotype, including expression of CD11b, CD11c, CD18, CD25, CD40, CD54, CD58, CD80, CD86, HLA class I, and HLA-DR as well as expression of CCR7 but not CCR5. The mature DC phenotype remained stable for at least 5 days in the absence of cytokines. Yield of DC was 14.0 +/- 4.7% and viability was 91.9 +/- 3.5%. Mature DCs effectively clustered with naive T cells and potently induced allogeneic T-cell proliferation and IL-2 and IFNgamma but not IL-4 production. Thus, this procedure allows large-scale generation of stably mature, Th1 responses inducing DCs under cGMP conditions in a closed system from cancer patients and is therefore well suited for immunotherapy.
Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes (2002)

Recent studies have implicated fatty acid-dependent activation of the serine kinase IKKβ, which plays a key role in tissue inflammation, in the pathogenesis of insulin resistance. High doses of salicylates have recently been shown to inhibit IKKβ activity and might therefore ameliorate insulin resistance and improve glucose tolerance in patients with type 2 diabetes. To test this hypothesis, we studied nine type 2 diabetic subjects before and after 2 weeks of treatment with aspirin (∼7 g/d). Subjects underwent mixed-meal tolerance tests and hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose to assess glucose turnover before and after treatment. High-dose aspirin treatment resulted in a ∼25% reduction in fasting plasma glucose, associated with a ∼15% reduction in total cholesterol and C-reactive protein, a ∼50% reduction in triglycerides, and a ∼30% reduction in insulin clearance, despite no change in body weight. During a mixed-meal tolerance test, the areas under the curve for plasma glucose and fatty acid levels decreased by ∼20% and ∼50%, respectively. Aspirin treatment also resulted in a ∼20% reduction in basal rates of hepatic glucose production and a ∼20% improvement in insulin-stimulated peripheral glucose uptake under matched plasma insulin concentrations during the clamp. In conclusion, these data support the hypothesis that IKKβ represents a new target for treating type 2 diabetes mellitus.
Novel Method of Synthesis of 5''-Phosphate 2'-O-ribosyl-ribonucleosides and Their 3'-Phosphoramidites (2013)

Synthesis of 5''-phosphate 2'-O-ribosylribonucleosides [Nr(p)] of four common ribonucleosides, and 3'-phosphoramidites of 5''-phosphate 2'-O-ribosyladenosine and 2'-O-ribosylguanosine using the H-phosphonate chemistry is described. An additional ring protected by benzoyl groups was incorporated into the main ribosyl ring in the reaction with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose in the presence of SnCl4. The obtained 2'-O-ribosylribonucleosides (Nr) were applied in the subsequent transformations with selective deprotection. Ethanolamine was applied as a very convenient reagent for selective removal of benzoyl groups. Additionally, the tetraisopropyldisiloxane-1,3-diyl (TIPDSi) group was found to be stable under these deprotection conditions. Thus, the selectively deprotected 5''-hydroxyl group of Nr was transformed into an H-phosphonate monoester which was found to be stable under the following conditions: the removal of the TIPDSi group with triethylammonium fluoride and the dimethoxytritylation of the 5''-hydroxyl function. The 5''-H-phosphonate of Nr precursors was easily transformed to the corresponding dicyanoethyl 5''-O-phosphotriesters before phosphitylation, which gave 3'-phosphoramidite units of Nr(p) in high yield. The derived phosphoramidite units were used in an automated oligonucleotide synthesizer to produce dimer Ar(p)T via the phosphoramidite approach. The obtained products were fully deprotected under standard deprotection conditions giving dimers with a 5''-phosphate monoester function. Application of an alkaline phosphatase to prove the presence of an additional phosphate group was described.
Soft synchronization of direct sequence spread-spectrum signals (1996)

A new technique for soft synchronization of direct-sequence spread-spectrum (DSSS) signals is presented. The technique, referred to as the dominant mode despreading (DMDS) algorithm, exploits the eigenstructure of a frequency-channelized DSSS signal to estimate the spreading code and underlying message sequence of the signal. Unlike other despreading techniques, the estimate of the code and data improves steadily with the number of code repeats. The technique is applicable to arbitrary spreading codes and message sequences and can operate in environments containing arbitrary levels of white background noise, and for signals with arbitrary unknown timing phase or carrier frequency offset. The technique requires the DSSS signal to have a constant-modulus spreading code and unrelated message and code-repeat rates. This paper introduces the basic technique, theoretically analyzes the algorithm to prove convergence under infinite time-average conditions, and demonstrates the algorithm via computer simulation for a single DSSS signal received in the presence of white Gaussian noise.
Site-specific interaction of vaccinia virus topoisomerase I with base and sugar moieties in duplex DNA. (1993)

Vaccinia DNA topoisomerase specifically binds and forms a covalent adduct at DNA sites containing a conserved sequence element 5'(C/T)CCTT decreases in the scissile strand. The molecular interactions that contribute to recognition of the CCCTT motif in a synthetic DNA substrate have been examined using modification interference, modification protection, and analog substitution techniques. We report that topoisomerase makes contact with guanine nucleotide bases of the pentamer motif complementary strand (3'GGGAA) within the major groove of the DNA helix and that alteration of the binding surface by chemical modification is deleterious to the interaction. Additional contacts are made with guanine residues located outside the pentamer element. The enzyme is unable to form a covalent adduct with synthetic RNA substrates. Analysis of the cleavage of DNA duplexes containing 2'OMe sugars suggests that the inability of the vaccinia topoisomerase to cleave either an RNA duplex or an RNA:DNA hybrid can be accounted for by the interfering effects of a 2' sugar substituent at two or more sites within the pentamer. Interaction with the sugar at the +2T nucleotide appears to be the most critical, as judged by the effects of single sugar substitutions.