gebhart/patrepeval huggingface dataset:
Virtual Screening Workflow Development Guided by the “Receiver Operating Characteristic” Curve Approach. Application to High-Throughput Docking on Metabotropic Glutamate Receptor Subtype 4 (2005)

The "receiver operating characteristic" (ROC) curve method is a well-recognized metric used as an objective way to evaluate the ability of a given test to discriminate between two populations. This facilitates decision-making in a plethora of fields in which a wrong judgment may have serious consequences including clinical diagnosis, public safety, travel security, and economic strategies. When virtual screening is used to speed-up the drug discovery process in pharmaceutical research, taking the right decision upon selecting or discarding a molecule prior to in vitro evaluation is of paramount importance. Characterizing both the ability of a virtual screening workflow to select active molecules and the ability to discard inactive ones, the ROC curve approach is well suited for this critical decision gate. As a case study, the first virtual screening workflow focused on metabotropic glutamate receptor subtype 4 (mGlu4R) agonists is reported here. Six compounds out of 38 selected and tested in vitro were shown to have agonist activity on this target of therapeutic interest.
Marine defaunation: Animal loss in the global ocean (2015)

Marine defaunation, or human-caused animal loss in the oceans, emerged forcefully only hundreds of years ago, whereas terrestrial defaunation has been occurring far longer. Though humans have caused few global marine extinctions, we have profoundly affected marine wildlife, altering the functioning and provisioning of services in every ocean. Current ocean trends, coupled with terrestrial defaunation lessons, suggest that marine defaunation rates will rapidly intensify as human use of the oceans industrializes. Though protected areas are a powerful tool to harness ocean productivity, especially when designed with future climate in mind, additional management strategies will be required. Overall, habitat degradation is likely to intensify as a major driver of marine wildlife loss. Proactive intervention can avert a marine defaunation disaster of the magnitude observed on land.
CS2: A Searchable Cryptographic Cloud Storage System (2011)

Cloud storage provides a highly available, easily accessible and inexpensive remote data repository to clients who cannot afford to maintain their own storage infrastructure. While many applications of cloud storage require security guarantees against the cloud provider (e.g., storage of high-impact business data or medical records), most services cannot guarantee that the provider will not see or modify client data. This is largely because the current approaches for providing security (e.g., encryption and digital signatures) diminish the utility and/or performance of cloud storage. This paper presents CS2, a cryptographic cloud storage system that guarantees confidentiality, integrity and verifiability without sacrificing utility. In particular, while CS2 provides security against the cloud provider, clients are still able not only to efficiently access their data through a search interface but also to add and delete files securely. The CS2 system is based on new highly-efficient and provably-secure cryptographic primitives and protocols. In particular, we (1) construct the first searchable symmetric encryption scheme that is adaptively secure, dynamic and achieves sub-linear search time; (2) introduce and construct search authenticators (which allow a client to efficiently verify the correctness of search operations); and (3) design an efficient and dynamic proof of data possession scheme. Based in part on our new constructions, we propose two cryptographic protocols for cloud storage which we prove secure in the ideal/real-world paradigm. The first protocol implements standard keyword search. Our second protocol implements what we refer to as assisted keyword search, where a user performs a keyword search, sees a summary of the results and asks for a subset of these results. Experimental results from an implementation of CS2 over both simulated and real-world data sets demonstrate that all operations achieve practical performance.
Neutral Atom Quantum Register (2004)

We demonstrate the realization of a quantum register using a string of single neutral atoms which are trapped in an optical dipole trap. The atoms are selectively and coherently manipulated in a magnetic field gradient using microwave radiation. Our addressing scheme operates with a high spatial resolution, and qubit rotations on individual atoms are performed with 99% contrast. In a final readout operation we analyze each individual atomic state. Finally, we have measured the coherence time and identified the predominant dephasing mechanism for our register.
<i>Streptococcus salivarius</i> Fimbriae Are Composed of a Glycoprotein Containing a Repeated Motif Assembled into a Filamentous Nondissociable Structure (2001)

Streptococcus salivarius, a gram-positive bacterium found in the human oral cavity, expresses flexible peritrichous fimbriae. In this paper, we report purification and partial characterization of S. salivarius fimbriae. Fimbriae were extracted by shearing the cell surface of hyperfimbriated mutant A37 (a spontaneous mutant of S. salivarius ATCC 25975) with glass beads. Preliminary experiments showed that S. salivarius fimbriae did not dissociate when they were incubated at 100 degrees C in the presence of sodium dodecyl sulfate. This characteristic was used to separate them from other cell surface components by successive gel filtration chromatography procedures. Fimbriae with molecular masses ranging from 20 x 10(6) to 40 x 10(6) Da were purified. Examination of purified fimbriae by electron microscopy revealed the presence of filamentous structures up to 1 microm long and 3 to 4 nm in diameter. Biochemical studies of purified fimbriae and an amino acid sequence analysis of a fimbrial internal peptide revealed that S. salivarius fimbriae were composed of a glycoprotein assembled into a filamentous structure resistant to dissociation. The internal amino acid sequence was composed of a repeated motif of two amino acids alternating with two modified residues: A/X/T-E-Q-M/phi, where X represents a modified amino acid residue and phi represents a blank cycle. Immunolocalization experiments also revealed that the fimbriae were associated with a wheat germ agglutinin-reactive carbohydrate. Immunolabeling experiments with antifimbria polyclonal antibodies showed that antigenically related fimbria-like structures were expressed in two other human oral streptococcal species, Streptococcus mitis and Streptococcus constellatus.
EDDY CURRENT SENSOR SYSTEM FOR NON-CONTACT SPEED AND DISTANCE MEASUREMENT OF RAIL VEHICLES (2000)

This paper deals with the concept and the performance of a new speed and distance measuring device for rail vehicles. The system consists of two eddy current sensors and a correlator. The sensors transform irregularities of the rail track (rail clamps) into two signals being similar but shifted by a transit time corresponding to the speed of the vehicle. The correlator extracts the transit time from the two sensor signals. The measuring system presented offers good accuracies with wide measurement ranges and good dynamical properties. Promising experimental tests were obtained in the laboratory as well as during several field tests.
Mesoscale Inhomogeneities in Aqueous Solutions of 3-Methylpyridine and Tertiary Butyl Alcohol (2011)

Motivated by controversies in the literature on the microscopic and mesoscopic structure of some aqueous solutions, we have performed static and dynamic light-scattering experiments in aqueous solutions of 3-methylpyridine (3MP) and tertiary butyl alcohol (TBA). In addition to the microscopic concentration fluctuations we have found the presence of reproducible mesoscopic inhomogeneities, which become especially pronounced below room temperature. We find that the observed inhomogeneities are near-spherical Brownian aggregates of a size from a hundred to a few hundred nm. We speculate that these aggregates are long-lived metastable clathrate-like precursors triggered by minute traces of impurities in these solutions.
Extraction and Characteristics of Anti-obesity Lipase Inhibitor from<i>Phellinus linteus</i> (2010)

To develop a potent anti-obesity lipase inhibitor from mushroom, the lipase inhibitory activities of various mushroom extracts were determined. Methanol extracts from Phellinus linteus fruiting body exhibited the highest lipase inhibitory activity (72.8%). The inhibitor was maximally extracted by treatment of a P. linteus fruiting body with 80% methanol at 40℃ for 24 hr. After partial purification by systematic solvent extraction, the inhibitor was stable in the range of 40~80℃ and pH 2.0~9.0. In addition to lipase inhibitory activity, the inhibitor showed 59.4% of superoxide dismutase-like activity and 56.3% of acetylcholinesterase inhibitory activity.
Photo-assisted local oxidation of GaN using an atomic force microscope (2006)

This paper introduces a photo-assisted atomic force microscope (AFM) local oxidation technique which is capable of producing highly smooth oxide patterns with heights reaching several tens of nanometres on both n- and p-types of GaN (and in principle on most semiconductors) without the use of chemicals. The novel methodology relies on UV illumination of the surface of the substrate during conventional AFM local oxidation. A low 1.2 V threshold voltage for n-type GaN was obtained, which can be explained by UV photo-generation of excess electron–hole pairs in the substrate near the junction, thereby reducing the electric field required to drive carrier flow through the tip–sample Schottky barrier. It was demonstrated that the presence or absence of light alone was sufficient to switch the growth of the oxide on or off. The photo-assisted AFM oxidation technique is of immediate interest to the semiconductor industry for the fabrication of GaN-based complementary metal–oxide–semiconductor devices and nanodevices, improves chances for AFM-type data storage, and presents new degrees of freedom for process control technique.
Specimen Charging on Thin Films with One Conducting Layer: Discussion of Physical Principles (2004)

Although the most familiar consequences of specimen charging in transmission electron microscopy can be eliminated by evaporating a thin conducting film (such as a carbon film) onto an insulating specimen or by preparing samples directly on such a conducting film to begin with, a more subtle charging effect still remains. We argue here that specimen charging is in this case likely to produce a dipole sheet rather than a layer of positive charge at the surface of the specimen. A simple model of the factors that control the kinetics of specimen charging, and its neutralization, is discussed as a guide for experiments that attempt to minimize the amount of specimen charging. Believable estimates of the electrostatic forces and the electron optical disturbances that are likely to occur suggest that specimen bending and warping may have the biggest impact on degrading the image quality at high resolution. Electron optical effects are likely to be negligible except in the case of a specimen that is tilted to high angle. A model is proposed to explain how both the mechanical and electron-optical effects of forming a dipole layer would have much greater impact on the image resolution in a direction perpendicular to the tilt axis, a well-known effect in electron microscopy of two-dimensional crystals.
Suppression of airway hyperresponsiveness induced by ovalbumin sensitisation and RSV infection with Y-27632, a Rho kinase inhibitor (2002)

These results suggest that the signalling pathway mediated through Rho kinase may have an important role in bronchial smooth muscle tone in allergen induced and virus induced AHR and should be considered as a novel target for asthma treatment.
The Lewy body variant of Alzheimer's disease (1990)

Thirty-six clinically diagnosed and pathologically confirmed Alzheimer's disease (AD) patients included 13 with cortical and subcortical Lewy bodies (LBs). The patients with LBs appeared to constitute a distinct neuropathologic and clinical subset of AD, the Lewy body variant (LBV). The LBV group showed gross pallor of the substantia nigra, greater neuron loss in the locus ceruleus, substantia nigra, and substantia innominata, lower neocortical ChAT levels, and fewer midfrontal tangles than did the pure AD group, along with a high incidence of medial temporal lobe spongiform vacuolization. Analysis of neuropsychological tests from 9 LBV subjects and 9 AD patients matched for age and degree of dementia revealed greater deficits in attention, fluency, and visuospatial processing in the LBV group. Similar comparisons of neurologic examinations showed a significant increase in masked facies; in addition there was an increase in essential tremor, bradykinesia, mild neck rigidity, and slowing of rapid alternating movements in the LBV group. Extremity rigidity, flexed posture, resting tremor, or other classic parkinsonian features were not characteristic of the LBV patient. In some cases, it may be possible to diagnose LBV premortem on the basis of the clinical and neuropsychological features.
Transient Knockdown of Tyrosine Hydroxylase during Development Has Persistent Effects on Behaviour in Adult Zebrafish (Danio rerio) (2012)

Abnormal dopamine (DA) signaling is often suggested as causative in schizophrenia. The other prominent hypothesis for this disorder, largely driven by epidemiological data, is that certain adverse events during the early stages of brain development increase an individual's risk of developing schizophrenia later in life. However, the clinical and preclinical literature consistently implicates behavioural, cognitive, and pharmacological abnormalities, implying that DA signaling is abnormal in the adult brain. How can we reconcile these two major hypotheses underlying much of the clinical and basic research into schizophrenia? In this study we have transiently knocked down tyrosine hydroxylase (TH, the rate limiting enzyme in DA synthesis) gene expression in the early stages of brain development in zebrafish using morpholinos. We show that by adulthood, TH and DA levels have returned to normal and basic DA-mediated behaviours, such as locomotion, are also normal. However, when they were exposed to a novel environment the levels of freezing and immediate positioning in deeper zones were significantly reduced in these adult fish. The neurochemistry underlying these behaviours is complex, and the exact mechanisms for these abnormal behaviours remains unknown. This study demonstrates that early transient alterations in DA ontogeny can produce persistent alterations in adult brain function and suggests that the zebrafish may be a promising model animal for future studies directed at clarifying the basic neurodevelopmental mechanisms behind complex psychiatric disease.
Thermochemistry of Aluminum Halides:  A Theoretical Appraisal (1998)

The Gaussian-2 (G2) ab initio procedure has been applied to gas-phase species of the formulas AlXn+, AlXYn+, and AlXYZn+ (n = 0, 1; X, Y, Z = F, Cl, Br). Existing thermochemical values for several of these species are highly uncertain, and many appear not to have been subjected to any previous study. The G2 results reported herein can be assessed against eight aluminum halides (namely AlF, AlCl, AlF+, AlFiCl3-i (i = 0−3), and AlBr3) whose enthalpies of formation are known to an accuracy of ±10 kJ mol-1 or better: in all cases, very good agreement is found between G2 and the literature values, while the literature values for several other species of uncertain thermochemistry are found to disagree with the G2 results despite large experimental uncertainties. In particular, we urge further experimental examination of the thermochemistry of AlF2, AlFCl, and AlCl2 and their molecular cations, for which the enthalpies of formation recommended in the JANAF thermochemical tables appear to be systematically too low.
Defective catabolism of oxidized LDL by J774 murine macrophages. (1992)

In J774 murine macrophages, chemically oxidized LDL (OxLDL) and biologically oxidized LDL (BioOxLDL) have similar metabolic fates, characterized by a relatively poor degradation when compared with acetylated LDL (AcLDL), and a modest ability to activate acyl-CoA:cholesterol acyltransferase (ACAT) (850 and 754 pmol [14C]oleate/mg cell protein in OxLDL- and BioOxLDL-incubated cells, versus 425 and 7070 pmol [14C]cholesteryl oleate/mg cell protein in control and AcLDL-incubated cells) with a massive increase of cellular free cholesterol. Therefore, OxLDL were used to investigate the cellular processing of oxidatively modified LDL. Binding and fluorescence microscopy studies demonstrated that OxLDL are effectively bound and internalized by macrophages and accumulate in organelles with density properties similar to those of endo/lysosomes. Although the overall metabolism of OxLDL is modestly affected by 100 microM chloroquine, owing to the poor cellular degradation of the substrate, the drug can further depress OxLDL degradation, indicating that this process takes place in an acidic compartment. Failure to detect products of extensive degradation of OxLDL in the medium is due to their relative resistance to enzymatic hydrolysis, as demonstrated also by in vitro experiments with partially purified lysosomal enzymes, rather than to the intracellular accumulation of degradation products (degraded intracellular protein is, at most, 8.5% of total). This sluggish degradation process is not due to a cytotoxic effect since OxLDL do not affect the intracellular processing of other ligands like AcLDL or IgG. The accumulation of OxLDL-derived products within macrophages may elicit cellular responses, the relevance of which in the atherosclerotic process remains to be addressed.
Combination of Adoptive Cell Transfer and Antibody Injection Can Eradicate Established Tumors in Mice–An<i>in vivo</i>study using anti-OX40mAb, anti-CD25mAb and anti-CTLA4mAb– (2009)

Boosting an effective immune response against established tumors remains a difficult challenge. This study shows the combination of 1) adoptive cell transfer using CD25 depleted splenocytes co-cultured with irradiated tumor cells, and 2) antibody injection therapy using CTLA4 blockade, the elimination of Treg and OX40, which together could eradicate an established MethA tumor in over 50% of the BALB/c mice. Each element of the protocol was shown to be necessary, as elimination of any factor except anti-CD25 antibody injection failed to eradicate the tumor.
A genetic local search hybrid architecture for VLSI circuit partitioning (2005)

During the last decade, the complexity and size of circuits have been rapidly increasing, placing a stressing demand on industry for faster and more efficient CAD tools for VLSI design. One major problem is the computational requirements for optimizing the place and route operations of a VLSI circuit. Thus, this paper investigates the feasibility of using reconfigurable computing platforms to improve the performance of CAD optimization algorithms for the VLSI circuit partitioning problem. The proposed reconfigurable computing genetic algorithm architecture achieved a five times speedup over conventional software implementation while maintaining 88% solution quality. Furthermore, a reconfigurable computing based hybrid algorithm improved upon this solution while using a fraction of the execution time required by the conventional software based approaches.
Interaction between human neutrophils and zymosan particles: the role of opsonins and divalent cations. (1981)

Abstract Human neutrophils were incubated with zymosan particles coated with either C3, IgG, or both. The cells formed rosettes with and ingested all 3 kinds of particle. Although C3-coated zymosan bound to about 80% of the neutrophils, the uptake of these particles was slow in comparison with IgG-coated or (C3 + lgG)-coated zymosan. All particles initiated an increase in the respiration of the cells as well as a specific release of lysosomal enzymes from the cells. IgG and C3 on zymosan reacted with different cell structures, as judged by the specific inhibition of F(ab’)-anti-lgG on the IgG-mediated reactions and of F(ab’)2-anti-C3 on the C3-mediated reactions. Moreover, trypsin treatment of the cells inhibited only the C3-mediated reactions. The binding of C3-coated zymosan and (C3 + IgG)-coated zymosan to the neutrophils was completely inhibited by addition of EDTA to or by omission of calcium and magnesium salts from the incubation medium. As a consequence, the ingestion of these particles and the stimulation of cell respiration and release of lysosomal enzymes was also strongly depressed under these conditions. In the presence of either calcium or magnesium ions, these reactions were suboptimally stimulated by zymosan coated with C3 or IgG + C3. In sharp contrast, IgG-coated zymosan and other IgG-coated material interacted with and stimulated the neutrophils in the absence as well as in the presence of divalent cations. The stimulation of neutrophil functions by phorbol myristate acetate did not require the presence of these ions either. Nonopsonized zymosan did not interact with the neutrophils during incubation in suspension. When centrifuged with the cells in a pellet, however, nonopsonized zymosan was ingested and induced a strong release of lysosomal enzymes but did not enhance the release of superoxide anions. Similar results were obtained when trypsin-treated cells were centrifuged with C3-coated zymosan. These reactions were inhibited by EDTA. The results indicate that: 1) Both IgG receptors and zymosan receptors on neutrophils mediate phagocytosis, stimulation of the respiratory burst, and initiation of lysosomal enzyme release; probably, C3 receptors only mediate binding of particles to neutrophils, a prerequisite for the interaction with the zymosan receptors. 2) Neutrophil functions are stimulated in the absence of extracellular divalent cations; therefore, influx of calcium ions into neutrophils is not required for neutrophil stimulation.
Characterization of intermediate hemoglobin produced during methemoglobin reduction by ascorbic acid. (1978)

Methemoglobin reduction by ascorbic acid was found apparently to cease halfway without further reduction. Studies by isoelectric focusing on Ampholine plate gel revealed that the solutions of the halfway reduced methemoglobin are composed of about 6% oxyhemoglobin, 59% intermediate hemoglobin, and 35% methemoglobin. The intermediate hemoglobin was isolated by CM Sephadex C-50 column chromatography and identified as alpha3+beta2+ valency hybrid by studies using the pattern of isoelectric focusing of p-chloromercuribenzoate-treated intermediate hemoglobin on Ampholine plate gel, absorption spectra, and difference spectra induced by the addition of inositol hexaphosphate in comparison with the reconstituted valency hybrids, alpha3+beta2+ and alpha2+beta3+. Essentially no alpha2+beta3+ valency hybrid was included in the intermediate hemoglobin solutions. These results suggest that methemoglobin reduction by ascorbic acid is mainly initiated by the attack of beta-methemoglobin chains accompanied by the following scheme. Methemoglobin leads to alpha3+beta2+ valency hybrid leads to oxyhemoglobin. The course of methemoglobin reduction by ascorbic acid through alpha2+beta3+ is likely to be small.