gebhart/patrepeval huggingface dataset:
Statins research unfinished saga: desirability versus feasibility (2005)

Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action (the so-called "class effect"). However, statins differ in multiple characteristics, including liver and renal metabolism, half-life, effects on several serum lipid components, bioavailability and potency. Some are fungal derivatives, and others are synthetic compounds. The percentage absorption of an oral dose, amount of protein binding, degree of renal excretion, hydrophilicity, and potency on a weight basis is variable. These differences may be even greater in diabetic patients, who may present diabetes-induced abnormalities in P450 isoforms and altered hepatic metabolic pathways. Thus, it is obvious that head-to-head comparisons between different statins are preferable than trial-to-trial comparisons. Such assessments are of utmost importance, especially in cases in which specific populations with a distinct lipid profile and altered metabolic pathways, like diabetics, are studied. It should be specially pinpointed that patients with metabolic syndrome and diabetes constitute also a special population regarding their atherogenic dyslipidemia, which is usually associated with low HDL-cholesterol, hypertriglyceridemia and predominance of small dense LDL-cholesterol. Therefore, these patients may benefit from fibrates or combined statin/fibrate treatment. This policy is not accomplished since in the real world things are more complex. Trials would require very large sample sizes and long-term follow-up to detect significant differences in myocardial infarction or death between two different statins. Moreover, the fact that new compounds are under several phases of research and development represents an additional drawback for performing the trials. Ideally, head-to-head trials regarding clinically important outcomes should be conducted for all drugs. Nonetheless, the desirability of performing such trials, which epitomize modern evidence-based medicine, is frequently superseded by the feasibility dictated by pragmatic and economic circumstances. In the latter case, in absence of solid systematic documentation of comparable health benefits and long-term safety, both researchers and practicing physicians should allude to the weight of scientific endorsement behind the arguments and seek for the possible strengths and weaknesses intrinsic to each specific study. In any case, conclusions based on surrogate endpoints cannot completely substitute head-to-head comparisons regarding patients' outcome.
Structure-Based Development of Novel Adenylyl Cyclase Inhibitors (2008)

In mammals, the second messenger cAMP is synthesized by a family of transmembrane isoforms (tmACs) and one known cytoplasmic enzyme, "soluble" adenylyl cyclase (sAC). Understanding the individual contributions of these families to cAMP signaling requires tools which can distinguish them. Here, we describe the structure-based development of isoform discriminating AC inhibitors. Docking calculations using a library of small molecules with the crystal structure of a sAC homologue complexed with the noncompetitive inhibitor catechol estrogen identified two novel inhibitors, 3,20-dioxopregn-4-en-21-yl4-bromobenzenesulfonate (2) and 1,2,3,4,5,6,7,8,13,13,14,14-dodecachloro-1,4,4a,4b,5,8,8a,12b-octahydro-11-sulfo-1,4:5,8-dimethanotriphenylene-10-carboxylic acid (3). In vitro testing revealed that 3 defines a novel AC inhibitor scaffold with high affinity for human sAC and less inhibitory effect on mammalian tmACs. 2 also discriminates between sAC and tmACs, and it appears to simultaneously block the original binding pocket and a neighboring interaction site. Our results show that compounds exploiting the catechol estrogen binding site can produce potent, isoform discriminating AC inhibitors.
Capturing and indexing computer-based activities with virtual network computing (2000)

Article Capturing and indexing computer-based activities with virtual network computing Share on Authors: Sheng Feng Li Department of Engineering, University of Cambridge, Cambridge, CB2 1PZ, UK Department of Engineering, University of Cambridge, Cambridge, CB2 1PZ, UKView Profile , Mark Spiteri Department of Engineering, University of Cambridge, Cambridge, CB2 1PZ, UK Department of Engineering, University of Cambridge, Cambridge, CB2 1PZ, UKView Profile , John Bates Department of Engineering, University of Cambridge, Cambridge, CB2 1PZ, UK Department of Engineering, University of Cambridge, Cambridge, CB2 1PZ, UKView Profile , Andy Hopper AT&T Laboratories Cambridge, 24a Trumpington Street, Cambridge, CB2 1QA, UK AT&T Laboratories Cambridge, 24a Trumpington Street, Cambridge, CB2 1QA, UKView Profile Authors Info & Claims SAC '00: Proceedings of the 2000 ACM symposium on Applied computing - Volume 2March 2000 Pages 601–603https://doi.org/10.1145/338407.338514Published:01 March 2000 16citation820DownloadsMetricsTotal Citations16Total Downloads820Last 12 Months4Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Modeling multi-step relevance propagation for expert finding (2008)

An expert finding system allows a user to type a simple text query and retrieve names and contact information of individuals that possess the expertise expressed in the query. This paper proposes a novel approach to expert finding in large enterprises or intranets by modeling candidate experts (persons), web documents and various relations among them with so-called expertise graphs. As distinct from the state of-the-art approaches estimating personal expertise through one-step propagation of relevance probability from documents to the related candidates, our methods are based on the principle of multi-step relevance propagation in topic specific expertise graphs. We model the process of expert finding by probabilistic random walks of three kinds: finite, infinite and absorbing. Experiments on TREC Enterprise Track data originating from two large organizations show that our methods using multi-step relevance propagation improve over the baseline one-step propagation based method in almost all cases.
Lipid lateral diffusion and membrane organization (1989)

It is shown that investigating the lateral motion of lipids in biological membranes can provide useful information on membrane lateral organization. After labeling membranes with extrinsic or intrinsic lipophilic fluorescent probes, fluorescence recovery after photobleaching experiments strongly suggests that specialized cells like spermatozoa, eggs and epithelia exhibit surface membrane regionalization or macrocompartmentation and that lateral microheterogeneities or lipid microdomains exist in the plasma membrane of many cellular systems.
Semantic locking in object-oriented database systems (1994)

Object-oriented databases are being increasingly used to model non-standard applications that emphasize modularity, composition, and rapid prototyping. A semantic locking protocol is presented for transaction management for such object-oriented databases. In particular, the protocol incorporates the semantics of complex objects, nested executions and dynamic conflicts resulting from referentially shared objects.
The cytoskeleton as a subcellular target of the antineoplastic drug lonidamine. (1993)

Lonidamine (LND), a dichlorinated derivative of indazole-3-carboxylic acid, has proved to exert a powerful antiproliferative effect and to impair the energy metabolism of normal and neoplastic cells. A target effect of the drug on the cell membrane structure was hypothesized. Thus, in order to elucidate better the mechanism of action of LND, the drug effects on the cell surface as well as on main cytoskeletal elements, i.e. actin microfilaments, microtubules and intermediate filaments, were investigated. In particular, an immunocytochemical and ultrastructural study was performed using two different cell lines: epithelial squamous carcinoma (A431) and melanoma (M14) cells. Treatment with 0.8 mM LND for 8 hr induced a remarkable rearrangement of the F-actin molecules with the disappearance of the stress fibers. As far as microtubules are concerned, formation of perinuclear patches of tubulin were detected after LND treatment. Intermediate filaments appeared to be differently affected by LND in the two cell types. Such changes were detected as an early phenomenon and the extent of the effects observed was positively related to the cell surface alterations and to the loss of cell viability, suggesting that the cytoskeletal elements might represent an additional target in the mechanisms of cytotoxic action of LND.
An Exposure‐Response Threshold for Lung Diseases and Lung Cancer Caused by Crystalline Silica (2011)

Whether crystalline silica (CS) exposure increases risk of lung cancer in humans without silicosis, and, if so, whether the exposure-response relation has a threshold, have been much debated. Epidemiological evidence is ambiguous and conflicting. Experimental data show that high levels of CS cause lung cancer in rats, although not in other species, including mice, guinea pigs, or hamsters; but the relevance of such animal data to humans has been uncertain. This article applies recent insights into the toxicology of lung diseases caused by poorly soluble particles (PSPs), and by CS in particular, to model the exposure-response relation between CS and risk of lung pathologies such as chronic inflammation, silicosis, fibrosis, and lung cancer. An inflammatory mode of action is described, having substantial empirical support, in which exposure increases alveolar macrophages and neutrophils in the alveolar epithelium, leading to increased reactive oxygen species (ROS) and nitrogen species (RNS), pro-inflammatory mediators such as TNF-alpha, and eventual damage to lung tissue and epithelial hyperplasia, resulting in fibrosis and increased lung cancer risk among silicotics. This mode of action involves several positive feedback loops. Exposures that increase the gain factors around such loops can create a disease state with elevated levels of ROS, TNF-alpha, TGF-beta, alveolar macrophages, and neutrophils. This mechanism implies a "tipping point" threshold for the exposure-response relation. Applying this new model to epidemiological data, we conclude that current permissible exposure levels, on the order of 0.1 mg/m³, are probably below the threshold for triggering lung diseases in humans.
Imaging and Analysis of OT1 T Cell Activation on Lipid Bilayers (2012)

Supported lipid bilayers are frequently used to study cell membrane protein dynamics during immune synapse formation by T cells. Here we describe methods for the imaging and analysis of OT1 + T cell activation and T-cell receptor \(TCR) dynamics on lipid bilayers.
Markov decision processes for train run curve optimization (2012)

We propose three computationally efficient methods for finding optimal run curves of electrical trains, all based on the idea of approximating the continuous dynamics of a moving train by a Markov Decision Process (MDP) model. Deterministic continuous train dynamics are converted to stochastic transitions on a discrete model by observing the similarity between the properties of convex combinations and those of probability mass functions. The resulting MDP uses barycentric coordinates to effectively represent the cost-to-go of the approximated optimal control problem. One of the three solution methods uses equal-distance steps, as opposed to the usual equal-time steps, to avoid self transitions of the MDP, which allows very fast computation of the cost-to-go in one pass only.
Paraxial Macrodystrophia Lipomatosa of the Medial Right Lower Limb (1991)

We report the orthopaedic management of a child with macrodystrophia lipomatosa of the medial aspect of the right lower limb. Bony and soft tissue overgrowth of the medial aspect of the lower limb resulted in valgus deformities at the subtalar joint, ankle, knee, and hip. The paraxial distribution, which has not been previously reported, suggests that the condition may be caused by alteration of somatic cells during limb bud development.
Shoot Development thorough Cytokinin Treatments in Ovary Culture of Three Interspecific Hybrid Lilies (2015)

본 연구는 나리 주요 품종의 종간교잡에서 생기는 삭과의 배유 퇴화방지와 미숙배 형성 시 발생하는 이상증상을 경감하기 위해 나리 종간교잡계통의 자방배양 했을 때 cytokinin 첨가가 신초형성에 미치는 영향을 구명하고자 하였다. FO계통은 BA 2.0 &#x338E;/L에서 신초 발생율이 18%로 가장 효과적이었고, BA 3.0 &#x338E;/L와 5.0 &#x338E;/L에서는 12%로 다소 저조한 결과였다. TDZ 첨가의 경우는 대조구와 같거나 비슷한 경향이었다. FA계통은 TDZ 첨가 시 대체적으로 신초형성율이 높았고 0.3 &#x338E;/L 처리가 효과적이었다. 반면 BA를 첨가한 배지에서는 14.3%에서 15.7%로 대조구와 큰 차이가 없었다. FLA계통에서 신초발생율은 생장조절제에 의해 증가되었으나 대조구 20%와 비교했을 때 BA 20~24%, TDZ 22~24%로 처리효과는 미미하였다. We performed the following experiment to increase the development of shoots in the in vitro culture of hybrid progeny. MS medium was used as the base medium; cytokinins BA at a concentration of 2.0, 3.0, or 5.0 &#x338E;/L and TDZ at a concentration of 0.2, 0.3, or 0.5 &#x338E;/L were added to the in vitro cultures. For the FO progeny, the shoot development rate was highest of 18% with 2.0 &#x338E;/L BA, at 18%, and 3.0 &#x338E;/L and 5.0 &#x338E;/L BA resulted in a lower rate of 12%. TDZ addition tended to identical or similar results to that of the control media. For the FA progeny, addition of TDZ tended to lead to a higher shoot development rate and was superior with 0.3 &#x338E;/L treatment. However, the addition of BA to the media resulted in a shoot development rate between 14.3% and 15.7%, similar to that of the control.
Logical dual concepts based on mathematical morphology in stratified institutions: applications to spatial reasoning (2019)

Several logical operators are defined as dual pairs, in different types of logics. Such dual pairs of operators also occur in other algebraic theories, such as mathematical morphology. Based on this observation, this paper proposes to define, at the abstract level of institutions, a pair of abstract dual and logical operators as morphological erosion and dilation. Standard quantifiers and modalities are then derived from these two abstract logical operators. These operators are studied both on sets of states and sets of models. To cope with the lack of explicit set of states in institutions, the proposed abstract logical dual operators are defined in an extension of institutions, the stratified institutions, which take into account the notion of open sentences, whose satisfaction is parametrised by sets of states. A hint on the potential interest of the proposed framework for spatial reasoning is also provided.
Optimum Combustion Control by TDLS200 Tunable Diode Laser Gas Analyzer (2010)

The TDLS200 laser gas analyzer, which is based on tunable diode laser spectroscopy, is a new generation of process analyzer. Characterized by high selectivity and long-term stability, it offers fast in-situ analysis of high-temperature or corrosive gas. This paper introduces the TDLS200’s real-time measurement of carbon monoxide in a furnace, its application for optimizing combustion control in the furnace, and its contribution to environmental preservation.
High Sensitivity of Glutamate Uptake to Extracellular Free Arachidonic Acid Levels in Rat Cortical Synaptosomes and Astrocytes (1992)

By using both synaptosomes and cultured astrocytes from rat cerebral cortex, we have investigated the inhibitory action of arachidonic acid on the high-affinity glutamate uptake systems, focusing on the possible physiological significance of this mechanism. Application of arachidonic acid (1-100 microM) to either preparation leads to fast (within 30 s) and largely reversible reduction in the uptake rate. When either melittin (0.2-1 microgram/ml), a phospholipase A2 activator, or thimerosal (50-200 microM), which inhibits fatty acid reacylation in phospholipids, is applied to astrocytes, both an enhancement in extracellular free arachidonate and a reduction in glutamate uptake are seen. The two effects display similar dose dependency and time course. In particular, 10% uptake inhibition correlates with 30% elevation in free arachidonate, whereas inhibition greater than or equal to 60% is paralleled by threefold stimulation of arachidonate release. In the presence of albumin (1-10 mg/ml), a free fatty acid-binding protein, inhibition by either melittin, thimerosal, or arachidonic acid is prevented and an enhancement of glutamate uptake above the control levels is observed. Our data show that neuronal and glial glutamate transport systems are highly sensitive to changes in extracellular free arachidonate levels and suggest that uptake inhibition may be a relevant mechanism in the action of arachidonic acid at glutamatergic synapses.
A Method for Reconstructing the Arterial Input Function during Helical CT: Implications for Myocardial Perfusion Distribution Imaging (2010)

The combination of bolus tracking and time-registered helical imaging enables reconstruction of the AIF during multidetector CT perfusion imaging. The helical CT AIF can be used to improve the semiquantitative assessment of myocardial perfusion distribution.
2‐DE proteome maps for the leaf apoplast of Nicotiana benthamiana (2010)

We provide 2-D gel reference maps for the apoplastic proteome of Nicotiana benthamiana leaves infiltrated or not with the bacterial gene vector Agrobacterium tumefaciens. About 90 proteins were analyzed by LC-MS/MS for identification and function assignment. We show, overall, an effective response of the plant to agroinfiltration involving a specific, cell wall maintenance-independent up-regulation of defense protein secretion. The proteome maps described should be a useful tool for systemic studies on plant-pathogen interactions or cell wall metabolism. They also should prove useful for the monitoring of secreted recombinant proteins and their possible pleiotropic effects along the cell secretory pathway of N. benthamiana leaves used as an expression platform for clinically useful proteins.
Resolution and noise properties of <sup>123</sup>I MIBG SPECT with collimator-detector response modeling (2011)

The effects of collimator-detector response (CDR) were studied for two clinical SPECT systems, the Siemens Symbia and GE Infinia, in terms of image resolution, noise properties, and activity estimation of <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">123</sup> I-MIBG in the heart. For each camera, Monte Carlo simulations were used to create CDR models, which were incorporated into a rotation-based projector for 3D-OS-EM SPECT reconstruction. The CDR models were used to generate simulated projections to study the degrading effects of the various CDR components, as well as the efficacy of compensating these components. In simulated images contaminated by <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">123</sup> I septal penetration and detector scatter, compensating the geometric response alone qualitatively restored image contrast, however, activity in the heart was significantly underestimated. The CDR models and the effect of CDR compensation were highly system-dependent. The contribution of detector scatter to activity underestimation was 8-10% for the Symbia and 18-20% for the Infinia, while the contribution of septal penetration was 30% for the Symbia and 5% for the Infinia. The simulation results were confirmed in SPECT measurements of a physical torso phantom on a Symbia SPECT/CT system. These results demonstrate that accurate activity estimation of cardiac <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">123</sup> IMIBG SPECT may require CDR compensation of septal penetration and detector scatter.
Structural and Magnetic Properties of Spinel Ferrite Epitaxial Films Pulsed-Laser-Deposited at Low Temperature (2001)

Thin films of NiZn- and MnZn-ferrites have been epitaxially grown on sapphire substrates at low temperatures by pulsed laser deposition (PLD). The structural and magnetic properties of the deposited films were investigated in detail. All films crystallized in the spinel phase even when deposited at room temperature and low oxygen pressures of 1 ×10 -4 Torr to 1 ×10 -6 Torr. X-ray diffraction analysis and atomic force microscopy showed that the spinel ferrite thin films grown at low temperatures below 200°C have high structural and morphological qualities, comparable to those of films grown at higher temperatures. The saturation magnetization of the room-temperature grown films was much lower than that of the bulk for NiZn-ferrite, while, for MnZn-ferrite, was 80% (270 emu/cm 3 ) of that of the bulk. These results make PLD a prime candidate technique for low-temperature epitaxial growth of ferrite thin films.
The separation of trypanosomes from blood by anion exchange chromatography: From Sheila Lanham’s discovery 50 years ago to a gold standard for sleeping sickness diagnosis (2019)

Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease that is fatal if untreated, caused by Trypanosoma brucei gambiense and T. brucei rhodesiense. In its 2012 roadmap, WHO targeted HAT for elimination as a public health problem in 2020 and for zero transmission in 2030. Diagnosis of HAT is a multistep procedure comprising of clinical suspicion, confirmation, and stage determination. Suspects are identified on clinical signs and/or on screening for specific antibodies. Parasitological confirmation of suspects remains mandatory to avoid unnecessary toxic drug administration. The positive predictive value of the antibody detection tests is low. Simple parasite detection techniques, microscopic examination of lymph node aspirate, or stained thick blood films lack sensitivity, whereas in T. brucei gambiense patients, the number of blood trypanosomes may be very low. Parasite concentration techniques are therefore indispensable. Half a century ago, Sheila Lanham discovered a technique to separate trypanosomes from the blood of infected rodents, based on anion exchange chromatography with diethyl amino ethyl (DEAE) cellulose, a weak anion exchanger. Between pH 6-9, trypanosome surface is less negatively charged than that of blood cells. When blood is poured on top of a DEAE cellulose column, blood cells are retained, whereas parasites pass the column together with the elution buffer. The result is a pure suspension of trypanosomes that retain their morphology and infectivity. Because cell surface charges vary among trypanosome and mammal species, the optimal buffer pH and ionic strength conditions for different combinations of host and trypanosome species were established. Lanham's technique revolutionized the diagnosis of HAT. It is indispensable in the production of the Card Agglutination Test for Trypanosomiasis (CATT), the most used field test for screening in T. brucei gambiense HAT foci and essential to confirm the diagnosis in suspected people. Lumsden and colleagues developed the mini anion exchange centrifugation technique (mAECT). After adaptation for field conditions, its superior diagnostic and analytical sensitivity compared to another concentration technique was demonstrated. It was recommended as the most sensitive test for demonstrating trypanosomes in human blood. At the beginning of the 21st century, the mAECT was redesigned, allowing examination of a larger volume of blood, up to 0.35 ml with whole blood and up to 10 ml with buffy coat. The plastic collector tube in the new kit is also used for detection of trypanosomes in the cerebrospinal fluid. Unfortunately, mAECT also has some disadvantages, including its price, the need to centrifuge the collector tube, and the fact that it is manufactured on a noncommercial basis at only two research institutes. In conclusion, 50 years after Sheila Lanham's discovery, CATT and mAECT have become essential elements in the elimination of HAT.