gebhart/patrepeval huggingface dataset:
Large-Scale Mutagenesis of the Yeast Genome Using a Tn7-Derived Multipurpose Transposon (2004)

We present here an unbiased and extremely versatile insertional library of yeast genomic DNA generated by in vitro mutagenesis with a multipurpose element derived from the bacterial transposon Tn7. This mini-Tn7 element has been engineered such that a single insertion can be used to generate a lacZ fusion, gene disruption, and epitope-tagged gene product. Using this transposon, we generated a plasmid-based library of approximately 300,000 mutant alleles; by high-throughput screening in yeast, we identified and sequenced 9032 insertions affecting 2613 genes (45% of the genome). From analysis of 7176 insertions, we found little bias in Tn7 target-site selection in vitro. In contrast, we also sequenced 10,174 Tn3 insertions and found a markedly stronger preference for an AT-rich 5-base pair target sequence. We further screened 1327 insertion alleles in yeast for hypersensitivity to the chemotherapeutic cisplatin. Fifty-one genes were identified, including four functionally uncharacterized genes and 25 genes involved in DNA repair, replication, transcription, and chromatin structure. In total, the collection reported here constitutes the largest plasmid-based set of sequenced yeast mutant alleles to date and, as such, should be singularly useful for gene and genome-wide functional analysis.
Customer care at Standard Life Assurance Co. Ltd (1995)

Investigates how Standard Life Assurance Co. Ltd learned to deal with customer care. Describes a mission introduced in 1992 which identified the company’s new determination to provide a quality of service that would fully meet the needs of the customers. A set of values and strategies were introduced to define a new sense of corporate direction, and lessons were learned from US companies. Ends by summarizing what has been learned over the past three years.
Rigid, Self‐Assembled Hydrogel Composed of a Modified Aromatic Dipeptide (2006)

A simple dipeptide self-assembles into a biocompatible hydrogel (see figure and inside cover). This novel biomaterial is extremely simple to prepare and has a remarkable rigidity. It is very stable under extreme conditions, can be injected, and can be shaped according to the vessel it has been assembled in. The hydrogel allows a wide variety of possible biomedical applications including tissue engineering, axonal regeneration, and controlled drug release.
Characterization of Deposition from Nasal Spray Devices Using A Computational Fluid Dynamics Model of The Human Nasal Passages (2007)

Many studies suggest limited effectiveness of spray devices for nasal drug delivery due primarily to high deposition and clearance at the front of the nose. Here, nasal spray behavior was studied using experimental measurements and a computational fluid dynamics model of the human nasal passages constructed from magnetic resonance imaging scans of a healthy adult male. Eighteen commercially available nasal sprays were analyzed for spray characteristics using laser diffraction, high-speed video, and high-speed spark photography. Steadystate, inspiratory airflow (15 L/min) and particle transport were simulated under measured spray conditions. Simulated deposition efficiency and spray behavior were consistent with previous experimental studies, two of which used nasal replica molds based on this nasal geometry. Deposition fractions (numbers of deposited particles divided by the number released) of 20- and 50-microm particles exceeded 90% in the anterior part of the nose for most simulated conditions. Predicted particle penetration past the nasal valve improved when (1) the smaller of two particle sizes or the lower of two spray velocities was used, (2) the simulated nozzle was positioned 1.0 rather than 0.5 or 1.5 cm into the nostril, and (3) inspiratory airflow was present rather than absent. Simulations also predicted that delaying the appearance of normal inspiratory airflow more than 1 sec after the release of particles produced results equivalent to cases in which no inspiratory airflow was present. These predictions contribute to more effective design of drug delivery devices through a better understanding of the effects of nasal airflow and spray characteristics on particle transport in the nose.
Secuelas «colaterales» no pretendidas de la LO 1/2015, de 30 de marzo, de reforma del Código Penal (2015)

La elevacion por la LO 1/2015, de 30 de marzo, del limite de duracion que determina la calificacion de la multa como pena leve o como pena menos grave, ha supuesto que, a partir de su entrada en vigor, al menos 16 figuras delictivas deban ser consideradas como delitos leves, y no como delitos menos graves, que es la calificacion que hasta la LO 1/2015 han tenido siempre, y que tengo la certidumbre de que el legislador no ha sido consciente de que tambien modificaba (como secuela colateral, no pretendida).
Increasing the throughput of HARQ via multi-packet transmission (2014)

In this work we consider incremental redundancy hybrid ARQ (HARQ) transmission of data packets over independent block-fading channels. In HARQ, the transmitter, upon request (NACK), resends the "NACKed" packet in the next available block. Conventionally, the original and retransmitted packets occupy one block, each. In our approach, we allow the transmitter to share the resources between the new and the retransmitted packets. To implement such a multi-packet transmission we consider the superposition coding and the timesharing modulation as possible encoding schemes for simultaneous transmission of both packets. Targeting the maximization of the throughput, we cast the problem into the framework of Markov decision process (MDP), where the decisions about the optimal transmission strategy are taken using information about the state of the receiver in the previous transmissions. Numerical examples obtained in a Rayleigh block-fading channel show that proposed transmission strategy provides notable gains over a conventional HARQ.
Recombinant human interleukin-3 stimulation of hematopoiesis in humans: loss of responsiveness with differentiation in the neutrophilic myeloid series (1988)

Recombinant human (rh) interleukin-3 (IL-3) stimulated the proliferation and differentiation of erythroid, granulocyte, macrophage, eosinophil (Eo), and mixed colonies as well as megakaryocytes from human bone marrow cells. rh IL-3 was a weaker stimulus than rh granulocyte-macrophage colony-stimulating factor (GM- CSF) for day 14 myeloid cell colonies. At day 7 of incubation, rh IL-3 stimulated a few G, M, and Eo clusters but no colonies. This loss of responsiveness of myeloid cells to rh IL-3 was accentuated with further differentiation of the cells. rh IL-3 stimulated very few or no clones after five-day incubation with enriched promyelocytes and myelocytes, whereas rh GM-CSF was an efficient stimulus. Responsiveness to rh IL-3 was completely lost in postmitotic mature neutrophils. Incubation of these cells with rh IL-3 did not result in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells or superoxide anion production after stimulation with formyl-methyl-leucyl-phenylalanine (FMLP), although they could be stimulated by rh GM-CSF. In addition, preincubation of neutrophils with different concentrations of rh IL-3 failed to increase or decrease their response to rh GM-CSF. In contrast to neutrophils, mature Eos could be stimulated by rh IL-3 to kill antibody-coated tumor cells. These results show that cells of the neutrophilic myeloid series lose their responsiveness to h IL-3 as they differentiate and suggest that although h IL-3 may be an important therapeutic agent to use for hematopoietic regeneration in vivo, the lack of stimulation of mature neutrophil function makes it an unlikely sole candidate as adjunct therapy for treatment of infectious diseases.
Molecular and Electronic Structures of Bis-(o-diiminobenzosemiquinonato)metal(II) Complexes (Ni, Pd, Pt), Their Monocations and -Anions, and of Dimeric Dications Containing Weak Metal−Metal Bonds (2003)

Two series of square planar, diamagnetic, neutral complexes of nickel(II), palladium(II), and platinum(II) containing two N,N-coordinated o-diiminobenzosemiquinonate(1-) pi radical ligands have been synthesized and characterized by UV-vis and (1)H NMR spectroscopy: [M(II)((2)L(ISQ))(2)], M = Ni (1), Pd (2), Pt (3), and [M(II)((3)L(ISQ))(2)] M = Ni (4), Pd (5), Pt (6). H(2)[(2)L(PDI)] represents 3,5-di-tert-butyl-o-phenylenediamine and H(2)[(3)L(PDI)] is N-phenyl-o-phenylenediamine; (L(ISQ))(1-) is the o-diiminobenzosemiquinonate pi radical anion, and (L(IBQ))(0) is the o-diiminobenzoquinone form of these ligands. The structures of complexes 1, 4, 5, and 6 have been (re)determined by X-ray crystallography at 100 K. Cyclic voltammetry established that the complete electron-transfer series consisting of a dianion, monoanion, neutral complex, a mono- and a dication exists: [M(L)(2)](z)z = -2, -1, 0, 1+, 2+. Each species has been electrochemically generated in solution and their X-band EPR and UV-vis spectra have been recorded. The oxidations and reductions are invariably ligand centered. Two o-diiminobenzoquinones(0) and two fully reduced o-diiminocatecholate(2-) ligands are present in the dication and dianion, respectively, whereas the monocations and monoanions are delocalized mixed valent class III species [M(II)(L(ISQ))(L(IBQ))](+) and [M(II)(L(ISQ))(L(PDI))](-), respectively. One-electron oxidations of 1 and trans-6 yield the diamagnetic dications [cis-[Ni(II)((2)L(ISQ))((2)L(IBQ))](2)]Cl(2) (7) and [trans-[Pt(II)((3)L(ISQ))((3)L(IBQ))](2)](CF(3)SO(3))(2) (8), respectively, which have been characterized by X-ray crystallography; both complexes possess a weak M.M bond and the ligands adopt an eclipsed configuration due to weak bonding interactions via pi stacking.
Inhibition of protein kinase C by cationic amphiphiles (1992)

A large number of PKC inhibitors are positively charged. We evaluated the structural features of cationic amphiphiles which are necessary for inhibiting PKC. Many of these compounds were derivatives of cholesterol, which possesses a hydrophobic backbone which does not perturb hydrocarbon packing in membrane bilayers. In addition, they contain a tertiary or quaternary nitrogen functionality in the head group. All designed cholesterol-based amphiphiles inhibit PKC activity; the potency of the amphiphile correlates with the presence of positive charge. Quaternary ammonium amphiphiles are 10-fold more potent than their tertiary amine counterparts, generally inhibiting in the 10-60 microM range using the Triton mixed micelle assay. Aside from charge, factors such as the structure of the amine-containing head group, its length from the hydrocarbon moiety, or the number of amine groups on the amphiphile did not markedly influence inhibitor potency. In contrast, the hydrocarbon backbone did influence potency: cationic amphiphiles containing a steroid backbone were more potent inhibitors of PKC than their straight-chain analogues. Changing the nature of the hydrocarbon from a sterol to an alkyl group lowers the pK of the amine head group so that the straight-chain analogues are no longer cationic in the conditions in the PKC assay. The results of these studies suggest that a combination of positive charge and a bilayer-stabilizing structural characteristic provides a basis for the rational design of PKC inhibitors.
Coating of cardiovascular stents with a semiconductor to improve their hemocompatibility. (1996)

Thrombogenesis on artificial surfaces can be described as an electron transfer reaction. To inhibit this oxidation process and thereby achieve high hemocompatibility, a surface requires semiconducting properties. However, because all known solid semiconductors are extremely brittle, the requirements for high hemocompatibility and mechanical stability cannot be met by any single material. Therefore, a hybrid design is introduced as a new approach to improve the hemocompatibility of cardiovascular stents.
Physical and Chemical Castration of Sex Offenders (1997)

ABSTRACT Castration, or removal of the testes, has been documented throughout history, occurring for a variety of social, punishment, and medical reasons. Currently, both “physical” and “chemical” castration are being hotly debated with respect to sex offenders, as the public and legislators are calling for actions to reduce sexual violence. Chemical castration has been proposed as a reversible alternative; its effectiveness, side-effects, risks, and recidivism rates have been studied extensively over the last 25 years. Physical castration, on the other hand, has been used primarily in Europe, has not been rigorously investigated, and remains a highly controversial and irreversible procedure. However, reported recidivism rates are strikingly better than those for chemical castration. Testosterone lowering therapy does offer a way to decrease and control the deviant sexual fantasies and urges of hard-core perpetrators. Ethical and scientific guidelines should be developed to investigate whether physical or chemical castration could be considered beneficial to the offender and to society.
Inflight Properties of NIF Ignition Capsules Inferred from Convergent Ablator Experiments (2012)

Convergent ablator (ConA) experiments on the National Ignition Facility (NIF) are indirect drive implosions that study the inflight dynamics of an imploding capsule. Side-on, back-lit radiography provides data used by the National Ignition Campaign to infer time-dependent properties of the capsule ablator, including its center of mass radius, velocity, unablated mass, shell thickness, and peak density. Previously, Callahan2 and Hicks reported ConA experiments demonstrating velocities approaching those required for ignition. Here, we present the findings from a full year of NIF ConA experiments where we have shot more than 20 targets at energies greater than 1 MJ to study the inflight dynamics of ignition-like implosions. These include:
Glucose metabolism in 'Sphingomonas elodea': pathway engineering via construction of a glucose-6-phosphate dehydrogenase insertion mutant (1995)

'Sphingomonas (formerly Pseudomonas) elodea' produces the industrially important polysaccharide gellan when grown in media containing glucose. Glucose catabolic enzymes and enzymes of central carbon metabolism were assayed in crude extracts of glucose-grown cultures of this bacterium. Based on these analyses it was concluded that glucose is converted to either gluconate or glucose 6-phosphate and that both of these products are converted to 6-phosphogluconate, a precursor for the Entner-Doudoroff (ED) and pentose phosphate pathways. Phosphoglucoisomerase (Pgi) activity was detected, but the lack of phosphofructokinase activity indicated that the Embden-Meyerhof glycolytic pathway is non-functional for glucose degradation. Thus, this bacterium utilizes glucose mainly via the ED and pentose phosphate pathways. Enzyme analyses suggested the involvement of glucose-6-phosphate dehydrogenase (Zwf) in glucose utilization and CO2 production. The zwf gene was cloned from 'S. elodea' and partially sequenced, and a null zwf mutant was constructed. This mutant exhibited no Zwf activity in in vitro assays, grew normally on glucose minimal medium and accumulated biomass (cells plus gellan) and produced CO2 at the same rates as the parental strain. Potential explanations for this finding are provided. Clones carrying the pgi gene were isolated fortuitously.
Large Slip of Aqueous Liquid Flow over a Nanoengineered Superhydrophobic Surface (2006)

While many recent studies have confirmed the existence of liquid slip over certain solid surfaces, there has not been a deliberate effort to design and fabricate a surface that would maximize the slip under practical conditions. Here, we have engineered a nanostructured superhydrophobic surface that minimizes the liquid-solid contact area so that the liquid flows predominantly over a layer of air. Measured through a cone-and-plate rheometer system, the surface has demonstrated dramatic slip effects: a slip length of approximately 20 microm for water flow and approximately 50 microm for 30 wt % glycerin. The essential geometrical characteristics lie with the nanoposts populated on the surface: tall and slender (i.e., needlelike) profile and submicron periodicity (i.e., pitch).
Impact of pH on Lactate Formation and Utilization by Human Fecal Microbial Communities (2007)

The human intestine harbors both lactate-producing and lactate-utilizing bacteria. Lactate is normally present at <3 mmol liter(-1) in stool samples from healthy adults, but concentrations up to 100 mmol liter(-1) have been reported in gut disorders such as ulcerative colitis. The effect of different initial pH values (5.2, 5.9, and 6.4) upon lactate metabolism was studied with fecal inocula from healthy volunteers, in incubations performed with the addition of dl-lactate, a mixture of polysaccharides (mainly starch), or both. Propionate and butyrate formation occurred at pH 6.4; both were curtailed at pH 5.2, while propionate but not butyrate formation was inhibited at pH 5.9. With the polysaccharide mix, lactate accumulation occurred only at pH 5.2, but lactate production, estimated using l-[U-(13)C]lactate, occurred at all three pH values. Lactate was completely utilized within 24 h at pH 5.9 and 6.4 but not at pH 5.2. At pH 5.9, more butyrate than propionate was formed from l-[U-(13)C]lactate in the presence of polysaccharides, but propionate, formed mostly by the acrylate pathway, was the predominant product with lactate alone. Fluorescent in situ hybridization demonstrated that populations of Bifidobacterium spp., major lactate producers, increased approximately 10-fold in incubations with polysaccharides. Populations of Eubacterium hallii, a lactate-utilizing butyrate-producing bacterium, increased 100-fold at pH 5.9 and 6.4. These experiments suggest that lactate is rapidly converted to acetate, butyrate, and propionate by the human intestinal microbiota at pH values as low as 5.9, but at pH 5.2 reduced utilization occurs while production is maintained, resulting in lactate accumulation.
A Rapid Vapor-Phase Acid (Hydrochloric Acid and Trifluoroacetic Acid) Hydrolysis of Peptide and Protein (1987)

A new method for the acid hydrolysis of protein is presented. Peptide bonds are cleaved by the action of an HCl/trifluoroacetic acid (TFA) vapor mixture. Contamination for the hydrolysis mixture is reduced to low levels (1-3 pmol). Recovery of hydrophobic amino acid is improved. Short reaction times are achieved and rapid removal of acids is facilitated. The reaction temperature is 158 degrees C for reaction times of 22.5 and 45 min with 7 M HCl and 10% TFA containing 0.1% phenol.
Structure and specificity of the RNA-guided endonuclease Cas9 during DNA interrogation, target binding and cleavage (2015)

CRISPR-associated endonuclease Cas9 cuts DNA at variable target sites designated by a Cas9-bound RNA molecule. Cas9's ability to be directed by single 'guide RNA' molecules to target nearly any sequence has been recently exploited for a number of emerging biological and medical applications. Therefore, understanding the nature of Cas9's off-target activity is of paramount importance for its practical use. Using atomic force microscopy (AFM), we directly resolve individual Cas9 and nuclease-inactive dCas9 proteins as they bind along engineered DNA substrates. High-resolution imaging allows us to determine their relative propensities to bind with different guide RNA variants to targeted or off-target sequences. Mapping the structural properties of Cas9 and dCas9 to their respective binding sites reveals a progressive conformational transformation at DNA sites with increasing sequence similarity to its target. With kinetic Monte Carlo (KMC) simulations, these results provide evidence of a 'conformational gating' mechanism driven by the interactions between the guide RNA and the 14th-17th nucleotide region of the targeted DNA, the stabilities of which we find correlate significantly with reported off-target cleavage rates. KMC simulations also reveal potential methodologies to engineer guide RNA sequences with improved specificity by considering the invasion of guide RNAs into targeted DNA duplex.
A Spindle Checkpoint Arrest and a Cytokinesis Failure by the Dominant-negative Polo-box Domain of Plk1 in U-2 OS Cells (2002)

Polo kinases play critical roles for proper M-phase progression. They are characterized by the presence of two regions of homology in the C-terminal non-catalytic domain, termed polo-box 1 (PB1) and polo-box 2 (PB2). Here we demonstrate that both PB1 and PB2 are required for targeting the catalytic activity of Plk1 to centrosomes, midbody, and kinetochores. Expression of either kinase-inactive PLK1/K82M or the C-terminal plk1 Delta N induced a pre-anaphase arrest with elevated Cdc2 and Plk1 activity. Prophase-arrested cells exhibited randomly oriented spindle structures, whereas metaphase cells exhibited aberrant bipolar spindles with Mad2 localization at kinetochores of misaligned chromosomes. Microtubule nucleation activity of centrosomes was not compromised. In vivo time-lapse studies revealed that expression of plk1 Delta N resulted in repeated cycles of bipolar spindle formation and disruption, suggestive of a defect in spindle stability. A prolonged arrest frequently led to the generation of micronucleated cells in the absence of sisterchromatid separation and centrosome duplication, indicating that micronucleation is not a result of accumulated cytokinesis failures. Interestingly, bypass of the mitotic arrest by dominant-negative spindle checkpoint components led to a failure in completion of cytokinesis. We propose that, in mammalian cells, the polo-box-dependent Plk1 activity is required for proper metaphase/anaphase transition and for cytokinesis.
Interactive visual comparison of multimedia data through type-specific views (2013)

Analysts who work with collections of multimedia to perform information foraging understand how difficult it is to connect information across diverse sets of mixed media. The wealth of information from blogs, social media, and news sites often can provide actionable intelligence; however, many of the tools used on these sources of content are not capable of multimedia analysis because they only analyze a single media type. As such, analysts are taxed to keep a mental model of the relationships among each of the media types when generating the broader content picture. To address this need, we have developed Canopy, a novel visual analytic tool for analyzing multimedia. Canopy provides insight into the multimedia data relationships by exploiting the linkages found in text, images, and video co-occurring in the same document and across the collection. Canopy connects derived and explicit linkages and relationships through multiple connected visualizations to aid analysts in quickly summarizing, searching, and browsing collected information to explore relationships and align content. In this paper, we will discuss the features and capabilities of the Canopy system and walk through a scenario illustrating how this system might be used in an operational environment.