gebhart/patrepeval huggingface dataset:
Single Amino Acid Mutations Alter the Distribution of Human Porphobilinogen Synthase Quaternary Structure Isoforms (Morpheeins) (2005)

Porphobilinogen synthase (PBGS) is an obligate oligomer that can exist in functionally distinct quaternary states of different stoichiometries, which are called morpheeins. The morpheein concept describes an ensemble of quaternary structure isoforms wherein different structures of the monomer dictate different multiplicities of the oligomer (Jaffe, E. K. (2005) Trends Biochem. Sci. 30, 490-497). Human PBGS assembles into long-lived morpheeins and has been shown to be capable of forming either a high activity octamer or a low activity hexamer (Breinig, S., Kervinen, J., Stith, L., Wasson, A. S., Fairman, R., Wlodawer, A., Zdanov, A., and Jaffe, E. K. (2003) Nat. Struct. Biol. 10, 757-763). All PBGS monomers contain an alphabeta-barrel domain and an N-terminal arm domain. The N-terminal arm structure varies among PBGS morpheeins, and the spatial relationship between the arm and the barrel dictates the different quaternary assemblies. We have analyzed the structures of human PBGS morpheeins for key interactions that would be predicted to affect the oligomeric assembly. Examples of individual mutations that shift assembly of human PBGS away from the native octamer are R240A and W19A. The alternate morpheeins of human PBGS variants R240A and W19A are chromatographically separable from each other and kinetically distinct; their structure and dynamics have been characterized by native gel electrophoresis, dynamic light scattering, and analytical ultracentrifugation. R240A assembles into a metastable hexamer, which can undergo a reversible conversion to the octamer in the presence of substrate. The metastable nature of the R240A hexamer supports the hypothesis that octameric and hexameric morpheeins of PBGS are very close in energy. W19A assembles into a mixture of dimers, which appear to be stable.
Selective cyclooxygenase 2 inhibitor NS-398 induces apoptosis in myeloma cells via a Bcl-2 independent pathway (2004)

NS-398, a selective inhibitor of cyclooxygenase 2 (COX-2), has been reported to inhibit growth and induce apoptosis in several cancer cell lines that overexpress COX-2. However it has not been extensively studied in multiple myeloma (MM). Here, we studied the effects of COX-2 inhibitors on MM cell lines and primary myeloma patient cells. We investigated the effects of NS-398 on proliferation and apoptosis in three myeloma cell lines (PCM6, U266 and RPMI8226) and isolated CD138-positive cells from MM patients. Furthermore, the combined effects of NS-398 plus dexamethasone (Dex) or thalidomide (Thal) were investigated. All myeloma cell lines express COX-2. NS-398 inhibited growth and induced apoptosis in PCM6, RPMI8226 and CD138-positive MM cells in a time- and dose-dependent manner. At low concentrations (10 microM), NS-398 primarily induced growth arrest without affecting cell viability, but at higher concentrations (over 25 microM), apoptosis was induced. During the process of apoptosis, the number of Fas-positive cells increased. Downstream signals of Fas, such as caspase 8, 3 and 9, were also activated. On the other hand, protein levels of the Bcl-2 family did not change, although mitochondrial transmembrane potential ((Delta)(psi)m) was decreased. Combined incubation with Dex or Thal enhanced NS-398-induced growth inhibition and apoptosis in RPMI8226 cells. The combined effect of Dex was more potent than that of Thal. Our findings suggests that COX-2 plays an important role in regulation of apoptosis in myeloma cells, and COX-2 inhibitors might serve as an effective tool for future chemoprevention and/or treatment of myeloma.
Constitutive expression of osteoclast-stimulating activity by normal clonal osteoblast-like cells: effects of parathyroid hormone and 1,25-dihydroxyvitamin D3. (1992)

Osteoblasts are known to produce osteoclast-stimulating activity (OSA). The aim of the current study was to relate the expression of OSA to the osteoblastic phenotype and examine its regulation by calciotropic hormones. The study was performed with the normal osteoblastic cell clone CRP 10/30 and the preosteoblastic clone CRP 4/7. OSA was determined with the well described isolated osteoclast pit assay, using sperm whale dentine as substrate. In contrast to previous studies, the assay was carried out at pH 7.36, rather than at pH 6.4 or 6.9. The results indicate that over 24 h, CRP 10/30 cells produce constitutively OSA, which compared to controls corresponds to an about 7-fold increase in resorption pits. There was considerably less activity expressed by either CRP 4/7 cells or fibroblasts. OSA proved to be heat labile, and its mol wt was estimated to be over 10 kilodaltons. While PTH-(1-34) did not influence the synthesis of OSA, the number of pits formed by osteoclasts incubated with medium conditioned by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-treated CRP 10/30 cells was increased 3-fold above baseline values. A similar increase was obtained with 1.25-(OH)2D3 added directly to CRP 10/30-conditioned medium. These results could not be duplicated with 1,25-(OH)2D3 added to either control medium or medium conditioned by CRP 4/7 cells or fibroblasts. The present study shows that normal clonal bone cells synthesize constitutively OSA, which is not regulated by PTH or 1,25-(OH)2D3. Furthermore, the results suggest that the synthesis of bone cell-derived OSA is limited to cells expressing the mature osteoblastic phenotype. Finally, CRP 10/30-conditioned medium appears to permit 1,25-(OH)2D3 to function on osteoclasts.
Experimental validation of wideband piezoelectric energy harvesting based on frequency-tuning synchronized charge extraction (2018)

International audience
On combinatorial auction and Lagrangean relaxation for distributed resource scheduling (1999)

Most existing methods for scheduling are based on centralized or hierarchical decision making using monolithic models. In ihis study, we investigate a new method based on a distributed and locally autonomous decision structure using the notion of combinatorial auction. In combinatorial auction the bidders demand a combination of dependent objects with a single bid. We show that not only can we use this auction mechanism to handle complex resource scheduling problems, but there exist strong links between combinatorial auction and Lagrangean-based decomposition. Exploring some of these properties, we characterize combinatorial auction using auction protocols and payment functions. This study is a first step toward developing a distributed scheduling framework that maintains system-wide performance while accommodating local preferences and objectives. We provide some insights to this framework by demonstrating four different versions of the auction mechanism using job shop scheduling problems.
CDSfold: an algorithm for designing a protein-coding sequence with the most stable secondary structure (2015)

Supplementary data are available at Bioinformatics online.
The new National Credit Act : some implications for municipalities (2006)

Extracted from text ... 8 IMFO ? Spring 2006 Incidental Credit It is not possible to discuss all the implications of the Act in this contribution; only some important aspects are highlighted. The normal water and electricity accounts sent out by municipalities would normally fall within the scope of section 4(6)(b) of the Act that provides as follows: Application of Act 4. (6) Despite any other provision of this Act- (b) if an agreement provides that a supplier of a utility or other continuous service- (i) will defer payment by the consumer until the supplier has provided a periodic statement of account for that ..
Permeation Process of Small Molecules across Lipid Membranes Studied by Molecular Dynamics Simulations (1996)

The transport of small molecules across a phospholipid membrane is studied by molecular dynamics simulations. The effects of size, hydrophobicity, and asphericity of the penetrants on the permeation process are investigated. For this purpose, permeability coefficients of oxygen and ammonia are computed using an inhomogeneous solubility−diffusion model and compared to the previously computed results of the permeation of water. Furthermore, solubility and diffusion data are computed for a series of Lennard-Jones particles that differ in size and shape. The results are discussed within the framework of the four-region model and are especially related to the free volume characteristics of the membrane. It is concluded that the free energy of solvation mainly determines the shape of the permeation resistance profile. For hydrophobic particles the membrane interior will act as a trap instead of a barrier. Moderately hydrophilic and hydrophilic penetrants experience the largest resistance to permeation in the dense part of the lipid tail region. This region is therefore most important in discriminating between various penetrants.
3,3'-Ethylenediglutarimide as a potential tumor inhibitor (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticle3,3'-Ethylenediglutarimide as a potential tumor inhibitorDavid B. Haydock and Thomas P. C. MulhollandCite this: J. Med. Chem. 1972, 15, 4, 447–448Publication Date (Print):April 1, 1972Publication History Published online1 May 2002Published inissue 1 April 1972https://pubs.acs.org/doi/10.1021/jm00274a044https://doi.org/10.1021/jm00274a044research-articleACS PublicationsRequest reuse permissionsArticle Views76Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Molecular Analysis of the Interaction of the Snake Venom Rhodocytin with the Platelet Receptor CLEC-2 (2011)

The Malayan pit viper, Calloselasma rhodostoma, produces a potent venom toxin, rhodocytin (aggretin) which causes platelet aggregation. Rhodocytin is a ligand for the receptor CLEC-2 on the surface of platelets. The interaction of these two molecules initiates a signaling pathway which results in platelet activation and aggregation. We have previously solved the crystal structures of CLEC-2 and of rhodocytin, and have proposed models by which tetrameric rhodocytin may interact with either two monomers of CLEC-2, or with one or two copies of dimeric CLEC-2. In the current study we use a range of approaches to analyze the molecular interfaces and dynamics involved in the models of the interaction of rhodocytin with either one or two copies of dimeric CLEC-2, and their implications for clustering of CLEC-2 on the platelet surface.
MonitR®: A Mobile Application for Monitoring Online Accounts' Security (2018)

As the internet grows, there is a rise in the dangers online accounts encounter whose potential harm can be severe. Online account users might use their accounts for various purposes such as: shopping, banking, social media and several other things. Usability is mostly the only concerned output; leaving the security of these accounts as an afterthought. A user's account might be compromised and misused by an attacker with various motivations ranging from financial to just having fun. One of the dangers that online users face when they sign up for accounts is impersonation. This paper presents a novel approach that gives users control of their account login and usage by creating a mobile application that monitors activities on a user's account. In so doing, the application can be able to decipher a fraudulent user from a legitimate user and send notification reports to legitimate users whenever there is a compromise from a malicious user. The application collects information such as location account is logged in from, device used for logging in, operating system, date and time of log in. Using the user's current location and following a set of fraud rules set by the user, reports are generated whenever the account is compromised. The user can then take action, like block device, set a geofence to control logging or lock account. The result of this approach is to prevent impersonations in online accounts and allow the user to set his/her own security policies.
Al<sub>2</sub>O<sub>3</sub>-Supported Mixed-Metal Oxides for Destructive Oxidation of (CH<sub>3</sub>)<sub>2</sub>S<sub>2</sub> (1997)

CuO/γ-Al2O3 is confirmed as the most active catalyst among eight γ-Al2O3-supported single metal oxides for the destructive oxidation of (CH3)2S2. To investigate the promoting effect, nine different metal oxides were separately added to CuO/γ-Al2O3. The experiments reveal MoO3 as the most effective promoter and the optimal added amount as around 10 wt %. Thermograms of TPR and spectra of XRD, employed to characterize the surface properties of a CuO−MoO3/γ-Al2O3 catalyst, verify that the addition of molybdenum oxide inhibits the growth of copper oxide crystal but may cause the formation of Cu3Mo2O9 and CuMoO4 phases. A CuO−MoO3/γ-Al2O3 catalyst exhibits higher activity and improved resistance to deactivation by sulfur compounds than does a commercial platinum catalyst. Since CH3SH may be easily converted into (CH3)2S2, the above-mentioned catalysts are decidedly effective in treating waste gas containing CH3SH.
Sump-Controlled Water Table Management Predicted with DRAINMOD (1989)

ABSTRACT Fluctuations in depth of the water table midway between subsurface-drainage/subirrigation conduits in a sump-controlled water table management system were predicted within an average deviation of 8 cm in DRAINMOD simulations conducted for a Commerce silt loam soil in the Mississippi Delta. The average daily sump water level from a field experiment was used as a model input to establish changes in the drainage outlet water level boundary conditions.
Overcoming the 2π ambiguity in low-coherence interferometric differential phase measurements (2001)

Quantitative phase measurements by optical coherence tomography and low coherence interferometry are restricted by the well known 2(pi) ambiguity to path length differences smaller than +/- (lambda) /2. We present a method that can overcome this ambiguity. We introduce a slight imbalance of dispersive material between the reference and sample arms of the interferometer. Thereby, short and long wavelengths of the source spectrum are separated within the signature of the interferometric signal. This causes a varying phase slope within the signal. To measure phase differences between two adjacent beams traversing a sample, the total interferometric signal of the two beams is recorded. The phase difference is calculated by subtracting the phase values obtained for both recorded signals. Without dispersive effects, the phase difference is constant across the coherence envelope. With the dispersive effect, the phase difference varies (because of the varying phase slopes) as a function of position within the interferometric signal. The slope of the phase difference between the two signals is proportional to the optical path difference, without 2(pi) ambiguity.
Synthetic Proteins Potently and Selectively Bind the Oncoprotein Gankyrin, Modulate Its Interaction with S6 ATPase, and Suppress Gankyrin/MDM2-Dependent Ubiquitination of p53 (2015)

Overexpression of the ankyrin repeat oncoprotein gankyrin is directly linked to the onset, proliferation, and/or metastasis of many cancers. The role of gankyrin in multiple disease-relevant biochemical processes is profound. In addition to other cellular processes, gankyrin overexpression leads to decreased cellular levels of p53, through a complex that involves MDM2. Thus, inhibition of this interaction is an attractive strategy for modulating oncogenic phenotypes in gankyrin-overexpressing cells. However, the lack of well-defined, hydrophobic, small-molecule binding pockets on the putative ankyrin repeat binding face presents a challenge to traditional small-molecule drug discovery. In contrast, by virtue of their size and relatively high folding energies, synthetic gankyrin-binding proteins could, in principle, compete with physiologically relevant PPIs involving gankyrin. Previously, we showed that a shape-complementary protein scaffold can be resurfaced to bind gankyrin with moderate affinity (KD ∼6 μM). Here, we used yeast display high-throughput screening, error-prone PCR, DNA shuffling, and protein engineering to optimize this complex. The best of these proteins bind gankyrin with excellent affinity (KD ∼21 nM), selectively co-purifies with gankyrin from a complex cellular milieu, modulates an interaction between gankyrin and a physiological binding partner (S6 ATPase), and suppresses gankyrin/MDM2-dependent ubiquitination of p53.
Battery health prediction under generalized conditions using a Gaussian\n process transition model (2018)

Accurately predicting the future health of batteries is necessary to ensure reliable operation, minimise maintenance costs, and calculate the value of energy storage investments. The complex nature of degradation renders data-driven approaches a promising alternative to mechanistic modelling. This study predicts the changes in battery capacity over time using a Bayesian non-parametric approach based on Gaussian process regression. These changes can be integrated against an arbitrary input sequence to predict capacity fade in a variety of usage scenarios, forming a generalised health model. The approach naturally incorporates varying current, voltage and temperature inputs, crucial for enabling real world application. A key innovation is the feature selection step, where arbitrary length current, voltage and temperature measurement vectors are mapped to fixed size feature vectors, enabling them to be efficiently used as exogenous variables. The approach is demonstrated on the open-source NASA Randomised Battery Usage Dataset, with data of 26 cells aged under randomized operational conditions. Using half of the cells for training, and half for validation, the method is shown to accurately predict non-linear capacity fade, with a best case normalised root mean square error of 4.3%, including accurate estimation of prediction uncertainty.
Learning Linear Dynamical Systems via Spectral Filtering (2017)

We present an efficient and practical algorithm for the online prediction of discrete-time linear dynamical systems with a symmetric transition matrix. We circumvent the non-convex optimization problem using improper learning: carefully overparameterize the class of LDSs by a polylogarithmic factor, in exchange for convexity of the loss functions. From this arises a polynomial-time algorithm with a near-optimal regret guarantee, with an analogous sample complexity bound for agnostic learning. Our algorithm is based on a novel filtering technique, which may be of independent interest: we convolve the time series with the eigenvectors of a certain Hankel matrix.
A sensitivity comparison of the Quick and Owren prothrombin time methods in oral anticoagulant therapy (2009)

Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). According to the World Health Organization recommendation, International Normalized Ratio (INR) results obtained from the same patient samples with the major PT methods (Quick and Owren) should be the same when the therapeutic range is the same. In our study blood samples were obtained from 207 OAT patients. We analyzed the samples using two Quick and two Owren PT (combined thromboplastin) reagents for INR and assessed the sensitivity and true coagulation activity using a new-generation PT method. The INR values with the Quick PT and Owren PT methods were very similar around the normal range, while unacceptable differences were seen within the therapeutic range and at higher INR values. The Quick PT results as INR are clearly lower than those given by Owren PT and the difference increases toward higher INR. The new PT method functions well with both Owren PT reagents, and we can calculate the true active INR. The Quick PT methods show no sensitivity to coagulation inhibition measurement. The harmonization of the INR is an important goal for the safety of OAT patients. More accurate INR results reduce morbidity and mortality, and the therapeutic ranges should be similar worldwide. In this study we found unacceptable differences in INR results produced by the two PT methods. The new method showed a lack of sensitivity to Quick PT. For the global harmonization of OAT therapy and for INR accuracy only the more sensitive Owren PT method should be used.
Contributory Role of Matrix Metalloproteinases in Cardiovascular Remodeling (2001)

Changes in cardiovascular tissue structure can result in alterations in function. This process occurs as a continuum and can be defined as cardiovascular remodeling. A family of zinc dependent proteases known as the matrix metalloproteinases (MMPs) has been demonstrated to cause tissue remodeling. A number of past studies have demonstrated increased expression and activation of MMPs in both myocardial and vascular remodeling processes. Experimental results support the concept that the MMPs directly contribute to progressive myocardial remodeling post-myocardial infarction and in cardiomyopathic disease. Within the vascular compartment, compelling evidence exists for the contributory role of MMPs in atheromatous plaque rupture and aortic aneurysms. Therefore, the purpose of this review is to examine recent studies of this proteolytic system in the context of cardiovascular remodeling.
Macitentan for the treatment of pulmonary arterial hypertension (2014)

Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA) for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug-drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial.
Application development for touch-screen interfaces (2007)

Validerat; 20101217 (root)