gebhart/patrepeval huggingface dataset:
Receptor‐Based Virtual Screening and Biological Characterization of Human Apurinic/Apyrimidinic Endonuclease (Ape1) Inhibitors (2012)

The endonucleolytic activity of human apurinic/apyrimidinic endonuclease (AP endo, Ape1) is a major factor in maintaining the integrity of the genome. Conversely, as an undesired effect, Ape1 overexpression has been linked to resistance to radio- and chemotherapeutic treatments in several human tumors. Inhibition of Ape1 using siRNA or the expression of a dominant negative form of the protein has been shown to sensitize cells to DNA-damaging agents, including various chemotherapeutic agents. Therefore, inhibition of the enzymatic activity of Ape1 might result in a potent antitumor therapy. A number of small molecules have been described as Ape1 inhibitors; however, those compounds are in the early stages of development. Herein we report the identification of new compounds as potential Ape1 inhibitors through a docking-based virtual screening technique. Some of the compounds identified have in vitro activities in the low-to-medium micromolar range. Interaction of these compounds with the Ape1 protein was observed by mass spectrometry. These molecules also potentiate the cytotoxicity of the chemotherapeutic agent methyl methanesulfonate in fibrosarcoma cells. This study demonstrates the power of docking and virtual screening techniques as initial steps in the design of new drugs, and opens the door to the development of a new generation of Ape1 inhibitors.
Molecular modeling, synthesis, and structures of N-methylated 3,5-linked pyrrolin-4-ones toward the creation of a privileged nonpeptide scaffold (1999)

The molecular modeling, synthesis, and elucidations of the solid state and solution structures of N-methylated 3,5-linked bispyrrolin-4-ones are described. Prior investigations established that the 3,5-linked pyrrolin-4-one based scaffold can be incorporated into mimics of beta-sheet/beta-strands and into potent, orally bioavailable inhibitors of the HIV-1 protease. To extend the utility of this scaffold beyond that of the initially designed mimics of beta-sheet/beta-strands, we have now explored the structure of N-methylated pyrrolinones. Molecular modeling indicated that N-methylated bispyrrolinones could adopt three low-energy backbone conformations (ca. 165 degrees, 289 degrees, and 320 degrees). Upon their successful synthesis, structural elucidation both in the solid state and in solution revealed the existence of two of the three predicted backbone conformers (ca. 165 degrees and 289 degrees). Two structures were particularly noteworthy and completely unexpected. Mono-N-methyl bispyrrolinone (+)-1 self assembled in the solid state to form a novel helix, while the acetylene-linked dimer of (+)-1, designed to potentiate the observed helical array, instead associated via an intermolecular hydrogen bond in parallel columns. These serendipitous observations led us to speculate that the pyrrolinone moiety may in fact represent a privileged nonpeptide scaffold, able to mimic not only the extended beta-sheet/beta-strand conformation as initially targeted, but also diverse conformations including those analogous to beta-turns and helices. These seemingly unlimited conformations greatly expand the scope of this scaffold for the development of low-molecular weight ligands for biologically important macromolecules.
Finite hyperelements: A 4D geometrical framework using covariant bases and metric tensors (1995)

Abstract A method is presented to evaluate space‐time finite element matrices in a general 4D context. Unlike the classical Jacobian‐based ‘textbook’ approach, the method described herein uses curvilinear gradient operators to properly handle finite elements having fewer local dimensions (i.e. two or three) than the global embedding domain. This unconventional, but powerful, method is described in details and is illustrated by an application simulating 4D pure convection in a curved diverging‐converging flow field.
Integrin binding to fibronectin and vitronectin maintains the barrier function of isolated porcine coronary venules (2001)

Integrin-mediated endothelial cell-extracellular matrix adhesion plays a critical role in maintaining the structural integrity of microvascular walls. The aim of this study was to evaluate the impact of specific integrin extracellular domain binding to matrix fibronectin and vitronectin on the barrier function of intact microvascular endothelium. The apparent permeability coefficient of albumin was measured in isolated and perfused porcine coronary venules using a fluorescence ratioing technique with the aid of fluorescence microscopy. Inhibition of integrin binding to either fibronectin with GRGDdSP peptide or vitronectin with GPenGRGDSPCA peptide dose-dependently increased venular permeability by 2- to 3-fold. The effects were sustained for more than 60 min and were reversible upon clearance of the peptides. In contrast, the inactive control peptide GRADSP did not significantly affect venular permeability. Pretreatment of the venules with purified human fibronectin and vitronectin, respectively, prevented the hyperpermeability response to GRGDdSP and GPenGRGDSPCA. GRGDSP, a peptide that inhibits integrin binding to both fibronectin and vitronectin, produced an even higher permeability (4.5-fold) in venules than GRGDdSP or GPenGRGDSPCA alone, and the effect was blunted in vessels preincubated with both fibronectin and vitronectin. The results indicate the importance of integrin-matrix interaction in the physiological regulation of microvascular permeability. It is likely that both fibronectin and vitronectin binding to integrins contribute to the maintenance of endothelial barrier function in venules.
Fibronectin Regulates Latent Transforming Growth Factor-β (TGFβ) by Controlling Matrix Assembly of Latent TGFβ-binding Protein-1 (2005)

Latent transforming growth factor-beta-binding proteins (LTBPs) are extracellular matrix (ECM) glycoproteins that play a major role in the storage of latent TGF beta in the ECM and regulate its availability. Here we show that fibronectin is critical for the incorporation of LTBP1 and transforming growth factor-beta (TGF beta) into the ECM of osteoblasts and fibroblasts. Immunolocalization studies suggested that fibronectin provides an initial scaffold that precedes and patterns LTBP1 deposition but that LTBP1 and fibronectin are later localized in separate fibrillar networks, suggesting that the initial template is lost. Treatment of fetal rat calvarial osteoblasts with a 70-kDa N-terminal fibronectin fragment that inhibits fibronectin assembly impaired incorporation of LTBP1 and TGFbeta into the ECM. Consistent with this, LTBP1 failed to assemble in embryonic fibroblasts that lack the gene for fibronectin. LTBP1 assembly was rescued by full-length fibronectin and superfibronectin, which are capable of assembly into fibronectin fibrils, but not by other fibronectin fragments, including a 160-kDa RGD-containing fragment that activates alpha5beta1 integrins. This suggests that the critical event for LTBP1 assembly is the formation of a fibronectin fibrillar network and that integrin ligation by fibronectin molecules alone is not sufficient. Not only was fibronectin essential for the initial incorporation of LTBP1 into the ECM, but the continued presence of fibronectin was required for the continued assembly of LTBP1. These studies highlight a nonredundant role for fibronectin in LTBP1 assembly into the ECM and suggest a novel role for fibronectin in regulation of TGF beta via LTBP1 interactions.
A monoclonal antibody against a synthetic peptide reveals common structures among spectrins and α‐actinin (1987)

A monoclonal antibody (Mab) against a synthetic peptide, SEDYGKDL, corresponding to one conserved sequence in the chicken alpha-fodrin repeats reacts in immunoblotting with avian alpha-spectrin and alpha-fodrin, both mammalian spectrins and with mammalian alpha-fodrin. This Mab also reacts with alpha-actinin in both chicken and human cells. Our results confirm the previously detected structural homology between spectrins and alpha-actinin and implicate their common evolutionary origin.
Application of a Mixture Experimental Design in the Optimization of a Self‐Emulsifying Formulation with a High Drug Load (2004)

Response surface methodology (RSM) was applied to optimize the self-emulsifying drug delivery system (SEDDS) containing 25% (w/w) Drug A, a model drug with a high lipophilicity and low water solubility. The key objective of this study was to identify an optimal SEDDS formulation that: 1) possesses a minimum concentration of the surfactant and a maximum concentration of lipid and 2) generates a fine emulsion and eliminates large size droplets (> or = 1 microm) upon dilution with an aqueous medium. Three ingredient variables [PEG 400, Cremophor EL, and a mixture of glycerol dioleate (GDO), and glycerol monooleate (GMO)] were included in the experimental design, while keeping the other ingredients at a fixed level (25% Drug A, 6% ethanol, 3% propylene glycol, 4% water, and 2% tromethamine) in the SEDDS formulation. Dispersion performance of these formulations upon dilution with a simulated gastrointestinal fluid was measured, and the population of the large droplets was used as the primary response for statistical modeling. The results of this mixture study revealed significant interactions among the three ingredients, and their individual levels in the formulation collectively dictated the dispersion performance. The fitted response surface model predicted an optimal region of the SEDDS formulation compositions that generate fine emulsions and essentially eliminates large droplets upon dilution. The predicted optimal 25% Drug A-SEDDS formulations with the levels of Cremophor EL ranging from 40-44%, GDO/GMO ranging from 10-13%, and PEG 400 ranging from 2.7-9.0% were selected and prepared. The dispersion experiment results confirmed the prediction of this model and identified potential optimal formulations for further development. This work demonstrates that RSM is an efficient approach for optimization of the SEDDS formulation.
Involvement of caspase-2 long isoform in Fas-mediated cell death of human leukemic cells (2001)

Engagement of the plasma membrane receptor Fas can induce apoptosis of leukemic cells. Signaling through Fas requires the formation of a death-inducing signaling complex (DISC) that involves the cytoplasmic domain of Fas, the adaptor molecule FADD/MORT-1, and procaspase-8. The present study investigated whether another caspase, known as procaspase-2L, played a role in Fas-mediated cell death. A series of human leukemic variant cells was derived by stable transfection with a CASP2L antisense construct (CASP2L/AS). Specific down-regulation of procaspase-2L decreased the sensitivity of these cells to apoptosis induced by an agonistic anti-Fas antibody (Ab, clone CH11), as determined by studying DNA fragmentation, chromatin condensation, and externalization of phosphatidylserine on the plasma membrane. In leukemic cells transfected with an empty vector, anti-Fas Ab treatment activated caspase-8, decreased the expression of the BH3 domain-only protein Bid, triggered the release of cytochrome c from the mitochondria to the cytosol, and activated caspase-3. All these events could not be observed when CASP2L/AS cells were similarly treated with anti-Fas Abs. CASP2L/AS transfection did not inhibit the formation of the DISC and no direct interaction between procaspase-2L and either Fas or FADD or procaspase-8 was identified. Down-regulation of procaspase-2L inhibited anti-Fas Ab-mediated cleavage of c-FLIP (FLICE-inhibitory protein), a protein that interferes with the formation of a functional DISC. These results suggest that the long isoform of caspase-2 plays a role in the Fas-mediated pathway to cell death by contributing to caspase-8 activation at the DISC level.
Tunable optical add/drop components in silicon-oxynitride waveguide structures (2002)

Ultra-compact tunable add/drop components, based on the resonant coupler concept, are realized in high index-contrast silicon-oxynitride waveguides. Thermo-optic heaters are used to tailor and tune the filter characteristic.
Personalized Mobile App Recommendation (2015)

Recent years have witnessed a rapid adoption of mobile devices and a dramatic proliferation of mobile applications (Apps for brevity). However, the large number of mobile Apps makes it difficult for users to locate relevant Apps. Therefore, recommending Apps becomes an urgent task. Traditional recommendation approaches focus on learning the interest of a user and the functionality of an item (e.g., an App) from a set of user-item ratings, and they recommend an item to a user if the item's functionality well matches the user's interest. However, Apps could have privileges to access a user's sensitive resources ( e.g., contact, message, and location). As a result, a user chooses an App not only because of its functionality, but also because it respects the user's privacy preference. To the best of our knowledge, this paper presents the first systematic study on incorporating both interest-functionality interactions and users' privacy preferences to perform personalized App recommendations. Specifically, we first construct a new model to capture the trade-off between functionality and user privacy preference. Then we crawled a real-world dataset (16,344 users, 6,157 Apps, and 263,054 ratings) from Google Play and use it to comprehensively evaluate our model and previous methods. We find that our method consistently and substantially outperforms the state-of-the-art approaches, which implies the importance of user privacy preference on personalized App recommendations. Moreover, we explore the impact of different levels of privacy information on the performances of our method, which gives us insights on what resources are more likely to be treated as private by users and influence users' behaviors at selecting Apps.
Analysis on stator circulating current characteristics of turbo-generator under eccentric faults (2009)

Stator circulating current characteristics when under a normal running condition and an air-gap eccentric fault are respectively analyzed, with the analysis results experimentally verified on a SDF-9 fault simulating generator. Experiment results accord with the theory analysis results. In this paper, it firstly deduces the air-gap magnetic flux intensity of normal condition and air-gap eccentric fault, and gains the instantaneous electric potential equation of each stator parallel branch. Then the instantaneous electric potential difference between the two stator parallel branches is further deduced. Based on this, the corresponding air-gap eccentricity conditions are taken into account to detailedly analyze the harmonic components' characteristics of the circulating current and the changing trend between the circulating current harmonic components and the fault parameters. Finally, a diagnosis method for the combined faults based on the circulating current characteristics is put forward. The achievements in this paper are full of reference value and positive meaning for the combined fault diagnosis of air-gap eccentricity and rotor short circuit.
Pre-impact fall detection system using dynamic threshold and 3D bounding box (2017)

Fall prevention and detection system have to subjugate many challenges in order to develop an efficient those system. Some of the difficult problems are obtrusion, occlusion and overlay in vision based system. Other associated issues are privacy, cost, noise, computation complexity and definition of threshold values. Estimating human motion using vision based usually involves with partial overlay, caused either by direction of view point between objects or body parts and camera, and these issues have to be taken into consideration. This paper proposes the use of dynamic threshold based and bounding box posture analysis method with multiple Kinect cameras setting for human posture analysis and fall detection. The proposed work only uses two Kinect cameras for acquiring distributed values and differentiating activities between normal and falls. If the peak value of head velocity is greater than the dynamic threshold value, bounding box posture analysis will be used to confirm fall occurrence. Furthermore, information captured by multiple Kinect placed in right angle will address the skeleton overlay problem due to single Kinect. This work contributes on the fusion of multiple Kinect based skeletons, based on dynamic threshold and bounding box posture analysis which is the only research work reported so far.
Allelic polymorphism of the interleukin-1 receptor antagonist gene in patients with acute or stable presentation of ischemic heart disease. (1999)

These data do not show a clear-cut association between the allele 2 of this IL-1 Ra gene polymorphism and ischemic heart disease. Among patients with myocardial infarction, the increased allele 2 frequency in those of younger age and with higher levels of C-reactive protein merits further investigation.
1,3,4‐Thiazaphosphole (1985)

Neue einfache Heteroarene sind die Titelverbindungen 1 , die sich aus Thiocarbonsäureamiden über eine Alkylierung am Schwefel und eine nachfolgende Kondensation mit Phosphortrichlorid herstellen lassen. 1 , R=R′=Ph, kristallisiert isomorph mit dem N ‐Analogon. magnified image
Fiber-optic logic gate (1985)

Operation of a fiber-optic logic gate is demonstrated for the first time. The principle of operation is based upon the intensity-dependent polarization rotation in birefringent fibers. Using a birefringent fiber combined with polarizers in the crossed state, the ON/OFF state of an AND operation is clearly observed with an extinction ratio of approximately 10 dB. The fiber-optic logic gate would be a promising device for optical information processing in the future because of the feasibility of compact configuration and very fast-speed operation.
Increased power injection in multimode optical-fiber buses through mode-selective coupling (1985)

The number of stations that can be put on an optical-fiber data bus is usually limited by the total allowable attenuation between transmitter and receiver. A fundamental assumption in local-area network designs has been that a passive bus coupler must remove from the bus the same fraction of optical power that it injects from the local transmitter. This mandates very inefficient power injection to the bus and limits the total number of stations that can be put on the bus. By considering mode-selective passive optical couplers, I show that this limitation can be overcome in principle, and practically all the local power can be injected. Calculations indicate that this can lead to an increase in injected power of around 7 dB, and an almost doubling of the number of possible stations on the bus.
Structural Determination of Lipid-bound ApoA-I Using Fluorescence Resonance Energy Transfer (2000)

Based on the x-ray crystal structure of lipid-free Delta43 apoA-I, two monomers of apoA-I were suggested to bind to a phospholipid bilayer in an antiparallel paired dimer, or "belt orientation." This hypothesis challenges the currently held model in which each of the two apoA-I monomers fold as antiparallel alpha-helices or "picket fence orientation." When apoA-I is bound to a phospholipid disc, the first model predicts that the glutamine at position 132 on one apoA-I molecule lies within 16 A of glutamine 132 in the second monomer, whereas, the second model predicts glutamines at position 132 to be 104 A apart. To distinguish between these models, glutamine at position 132 was mutated to cysteine in wild-type apoA-I to produce Q132C apoA-I, which were labeled with thiol-reactive fluorescent probes. Q132C apoA-I was labeled with either fluorescein (donor probe) or tetramethylrhodamine (acceptor probe) and then used to make recombinant phospholipid discs (recombinant high density lipoprotein (rHDL)). The rHDL containing donor- and acceptor-labeled Q132C apoA-I were of similar size, composition, and lecithin:cholesterol acyltransferase reactivity when compared to rHDL-containing human plasma apoA-I. Analysis of donor probe fluorescence showed highly efficient quenching in rHDL containing one donor- and one acceptor-labeled Q132C apoA-I. rHDL containing only acceptor probe-labeled Q132C apoA-I showed rhodamine self-quenching. Both of these observations demonstrate that position 132 in two lipid-bound apoA-I monomers were in close proximity, supporting the "belt conformation" hypothesis for apoA-I on rHDL.
Data and Commands Communication Protocol for Neuromorphic Platform Configuration (2016)

In this paper, we present a new network protocol and methodology to enhance the configuration phase of the SpiNNaker spiking neural network hardware simulator. We have developed a system able to accept and process on-board a set of configuration primitives (data specification) encapsulated into ad-hoc packets, avoiding the management of chip memory from the host computer. We performed a study of the data specification generator implemented in the host software library. Afterwards, we extended the currently on-board data specification executor to cope with the newly-formed packets. The use of UDP protocol presents challenges due to its intrinsic unreliability. Furthermore, the presence of a single Ethernet link per board, and the requirement for a dedicated processor to handle all Ethernet communications limit the available communication bandwidth. A set of simulations was performed in order to tune the protocol parameters and to study the trade-offs between transmission speed and reliability. We were able to reach a throughput of a packet every 250 μs, which corresponds to a bandwidth of ~10 Mb/s. This system is able to open new perspectives for the SpiNNaker architecture. Thus, including the reduction of the time required to configure a simulation, the ability to configure more instances of a simulation. This system could even to enable the simulation of neurogenesis.
Algorithms for Identifying Boolean Networks and Related Biological Networks Based on Matrix Multiplication and Fingerprint Function (2000)

Due to the recent progress of the DNA microarray technology, a large number of gene expression profile data are being produced. How to analyze gene expression data is an important topic in computational molecular biology. Several studies have been done using the Boolean network as a model of a genetic network. This paper proposes efficient algorithms for identifying Boolean networks of bounded indegree and related biological networks, where identification of a Boolean network can be formalized as a problem of identifying many Boolean functions simultaneously. For the identification of a Boolean network, an O(mnD+1) time naive algorithm and a simple O (mnD) time algorithm are known, where n denotes the number of nodes, m denotes the number of examples, and D denotes the maximum in degree. This paper presents an improved O(momega-2nD + mnD+omega-3) time Monte-Carlo type randomized algorithm, where omega is the exponent of matrix multiplication (currently, omega < 2.376). The algorithm is obtained by combining fast matrix multiplication with the randomized fingerprint function for string matching. Although the algorithm and its analysis are simple, the result is nontrivial and the technique can be applied to several related problems.
Chemistry & theory of chromium deposition: Part II-Theory of deposition (1997)

In Part II, various theories of chromium electrodeposition, based on wide-ranging research, are discussed, and an effort is made to show the complexity of chromium deposition and that it is still not completely understood. Part I was published in the May 1997 issue of P&SF.