gebhart/patrepeval huggingface dataset:
Sulfated Pentagalloylglucoside Is a Potent, Allosteric, and Selective Inhibitor of Factor XIa (2013)

Inhibition of factor XIa (FXIa) is a novel paradigm for developing anticoagulants without major bleeding consequences. We present the discovery of sulfated pentagalloylglucoside (6) as a highly selective inhibitor of human FXIa. Biochemical screening of a focused library led to the identification of 6, a sulfated aromatic mimetic of heparin. Inhibitor 6 displayed a potency of 551 nM against FXIa, which was at least 200-fold more selective than other relevant enzymes. It also prevented activation of factor IX and prolonged human plasma and whole blood clotting. Inhibitor 6 reduced V(MAX) of FXIa hydrolysis of chromogenic substrate without affecting the K(M), suggesting an allosteric mechanism. Competitive studies showed that 6 bound in the heparin-binding site of FXIa. No allosteric small molecule has been discovered to date that exhibits equivalent potency against FXIa. Inhibitor 6 is expected to open up a major route to allosteric FXIa anticoagulants with clinical relevance.
An Overview of Blockchain Technology: Architecture, Consensus, and Future Trends (2017)

Blockchain, the foundation of Bitcoin, has received extensive attentions recently. Blockchain serves as an immutable ledger which allows transactions take place in a decentralized manner. Blockchain-based applications are springing up, covering numerous fields including financial services, reputation system and Internet of Things (IoT), and so on. However, there are still many challenges of blockchain technology such as scalability and security problems waiting to be overcome. This paper presents a comprehensive overview on blockchain technology. We provide an overview of blockchain architechture firstly and compare some typical consensus algorithms used in different blockchains. Furthermore, technical challenges and recent advances are briefly listed. We also lay out possible future trends for blockchain.
Ion Transport in Silica Nanocomposite Electrolytes (2003)

The ion-transport properties of composite electrolytes composed of oligomers of poly(ethylene glycol) dimethyl ether, hydrophobic fumed silica, and (LiTFSI) are investigated using nuclear magnetic resonance (NMR), electrophoretic NMR (ENMR), ac impedance spectroscopy, and rheology. The effects of fumed silica and salt concentration on ionic conductivity, diffusivity of ions and oligomers, and lithium transference number are examined at 30°C. The fumed silica forms a self- supporting network with large pores such that the network, regardless of silica concentration, has little effect on ion-transport characteristics. Examination of the effect of salt on ion transport reveals a maximum ionic conductivity at around 1.06 M, which is attributed to a tradeoff of adding more charge carriers balanced against increased ion-ion interactions and reduced mobilities. with respect to salt concentration surprisingly passes through a minimum around 0.35 M. The increase in at higher concentrations is attributed to the mobilities of cations, anions, and solvating oligomer becoming constrained to the same value due to "loss of free volume." The values of at low salt concentrations (<0.35 M) are attributed to the ions existing in either a fully dissociated state or primarily as charged complexes. Results of from ENMR and from estimation via pulse field gradient NMR (pfg-NMR) are compared showing that pfg-NMR consistently overestimates Finally, a comparison is presented of measured conductivity with that calculated from the Nernst-Einstein equation and diffusivities found from pfg-NMR measurement; we discuss possible reasons why it is inappropriate to estimate ion-pair formation by this comparison. © 2003 The Electrochemical Society. All rights reserved.
3.5- to 12-μm dual-band spectrometer (2004)

A new approach is described for obtaining spectral imagery over a broad range of infrared wavelengths, with high efficiency, and with a single grating element and focal plane array. The approach represents a simplification and mass reduction over the traditional approach involving multiple focal plane arrays, dispersing elements, and optical beamsplitters. The new approach has significant advantages for space-based hyperspectral imagers operating in the infrared over a broad range of wavelengths (e.g., MWIR and LWIR), where the reduction in cryocooled mass relative to the multichannel approach translates into noteworthy savings in cryocooling requirements and launch costs. Overlapping grating orders are focused onto a multiwaveband focal plane array to create spectral images of a scene simultaneously in multiple wavelength regions. The blaze of the grating is chosen so that all spectral orders are dispersed with high grating efficiency. Such an approach extends the spectral range of dispersive spectrometers to several octaves of wavelength, while preserving the compact packaging and cryogenic requirements of conventional (one octave) instruments. We conclude with a description of a ground-based demonstration of an MWIR and LWIR embodiment of the concept.
Improving 1,3-Propanediol Production from Glycerol in a Metabolically Engineered Escherichia coli by Reducing Accumulation of sn-Glycerol-3-phosphate (2002)

High levels of glycerol significantly inhibit cell growth and 1,3-propanediol (1,3-PD) production in anaerobic glycerol fermentation by genetically engineered Escherichia coli (E. coli) strains expressing genes from the Klebsiella pneumoniae dha (K.pneumoniae) regulon. We have previously demonstrated that 1,3-PD production by the engineered E. coli can be improved by reducing the accumulation of methylglyoxal. This study focuses on investigation of another lesser-known metabolite in the pathways related to 1,3-PD production-glycerol-3-phosphate (G3P). When grown anaerobically on glycerol in the absence of an exogenous acceptor, the engineered E. coli strains have intracellular G3P levels that are significantly higher than those in K. pneumoniae, a natural 1,3-PD producer. Furthermore, in the engineered E. coli strains, the G3P levels increase with increasing glycerol concentrations, whereas, in K. pneumoniae, the concentrations of G3P remain relatively constant. Addition of fumarate, which can stimulate activity of anaerobic G3P dehydrogenase, into the fermentation medium led to a greater than 30-fold increase in the specific activity of anaerobic G3P dehydrogenase and a significant decrease in concentrations of intracellular G3P and resulted in better cell growth and an improved production of 1,3-PD. This indicates that the low activity of G3P dehydrogenase in the absence of an exogenous electron acceptor is one of the reasons for G3P accumulation. In addition, spent media from E.coli Lin61, a glycerol kinase (responsible for conversion of glycerol to G3P) mutant, contains greatly decreased concentrations of G3P and shows improved production of 1,3-PD (by 2.5-fold), when compared to media from its parent strain E. coli K10. This further suggests that G3P accumulation is one of the reasons for the inhibition of 1,3-PD production during anaerobic fermentation.
Response of an in vivo-in vitro tumour to X-rays and cytotoxic drugs: effect of tumour disaggregation method on cell survival. (1980)

EMT-6/UW tumours were treated in vivo with X-rays, cyclophosphamide, or bleomycin. Cell survival was assayed in vitro following tumour disaggregation with trypsin or an enzyme cocktail (EC) consisting of pronase, collagenase and DNase which gives a 10-20 x higher cell yield. Surviving fraction was lower after cyclophosphamide treatment for cells isolated with EC than for cells prepared with trypsin. The opposite result was obtained with bleomycin; trypsin-isolated cells appeared more sensitive. In attempting to determine the basis for this discrepancy, it was found that both dissociation methods isolate a non-representative cell sample with fewer cells in DNA synthesis (12-13%) than in the original tumour (approximately 22%). The specific nature of the interaction between the injury caused by drug and enzyme remains to be elucidated.
Optical novelty filters (1989)

A novelty filter detects what is new in a scene and may be likened to a temporal high-pass filter. The current status of optical novelty filters and related devices, based upon four-wave mixing and two-beam coupling in photorefractive media, is reviewed. A detector that shows only what is not new, a monotony filter, may be likened to a temporal low-pass filter. Demonstrations of high- and low-pass and bandpass temporal image filters are then discussed. An analytical treatment of the two-beam coupling devices is given in a Laplace transform framework in the undepleted pump approximation assuming plane wave inputs. This allows a unified treatment of the various filter characteristics.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A laser‐light pulse counting method for automatic and sensitive counting of bacteria stained with acridine orange (1989)

A laser‐light pulse counting method was developed and investigated for its ability automatically to count acridine orange‐stained bacteria and microcolonies of bacteria on the surface of polycarbonate membrane filters. The system consisted of an Argon laser which delivered a 5 μm diameter spot of coherent 488 nm wavelength light which was raster scanned across a 5×2 mm area of the membrane. Fluorescence pulses of orange light ( ca 650 nm) were detected via a dichroic mirror and barrier filter with a photomultiplier tube. For microcolony preparations a good relationship between the number of light pulses and cell density down to below 10 2 /ml was observed, but at lower cell densities counting was not reliable, probably because of fluorescent debris. The method was also able to count single cells, but background auto‐fluorescence and photo‐bleaching produced a high and variable background signal in some samples.
A novel fully human monoclonal antibody against epidermal growth factor receptor (EGFR). First clinical and FDG-PET imaging results from a phase I/II trial conducted by the Danish Head and Neck Cancer Study Group (DAHANCA) in patients with squamous cell carcinoma of the head and neck (SCCHN) (2005)

5530 Background: The fully human IgG1κ monoclonal antibody 2F8 (HuMax-EGFr) targets the EGFR. 2F8 competitively inhibits ligand binding and ligand-induced receptor phosphorylation and it induces significant antibody-dependent cellular cytotoxicity in vitro. Methods: A phase I/II single dose escalation study followed by a repeat dose extension. 24 patients with histologically confirmed recurrent or metastatic SCCHN received i.v. infusions in doses of 0.15, 0.5, 1, 2, 4, or 8 mg/kg. Four patients were included at each dose level. At day 28 the single dose was followed by 4 weekly infusions at the same dose. The primary objective was safety. Efficacy was evaluated by FDG-PET and by CT-scans one week after last dose. Results: Data is presented from 24 patients. 6 patients were withdrawn prior to repeated dosing due to disease progression. No patients experienced dose limiting toxicities and maximum tolerated dose has not been reached. The frequency of acneiform rashes increased with dose. Hence, 7 of 8 patients receiving 4 or 8 mg/kg experienced rash. At these 2 dose levels, pharmacokinetic data showed constant clearance indicating saturation of compartments. Response evaluation by FDG-PET in 15 evaluable patients showed 6 partial metabolic responses (PMR) and 3 stable metabolic disease (SMD), all occurring in the 2, 4, and 8 mg/kg dose groups. In fact, all 8 patients at 4 or 8 mg/kg obtained PMR or SMD. Response evaluation by CT in 16 evaluable patients showed 2 patients with partial response and 8 with stable disease all occurring in the 1, 2, 4, and 8 mg/kg dose group. 6 out of 7 patients treated with 4 or 8 mg/kg thus obtained partial response or stable disease. Conclusions: 2F8 has a favorable safety profile in doses up to 8 mg/kg. Encouraging efficacy data using FDG-PET and CT imaging are demonstrated, particularly in the 4 and 8 mg/kg dose groups. The study is currently extended at the 8 mg/kg dose level. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genmab Genmab
Decision analysis for management judgment (2004)

Foreword / Lawrence D. Phillips -- How people make decisions involving multiple objectives -- Decisions involving multiple objectives: SMART -- Introduction to probability -- Decision making under uncertainty -- Decision trees and influence diagrams -- Applying simulation to decision problems -- Revising judgments in the light of new information -- Biases in probability assessment -- Methods for eliciting probabilities -- Risk and uncertainty management -- Decisions involving groups of individuals -- Resource allocation and negotiation problems -- Decision framing and cognitive inertia -- Scenario planning: an alternative way of dealing with uncertainty -- The analytic hierarchy process -- Alternative decision-support systems.
Control of Potassium: Distribution, Excretion, and Extracellular Concentration (2013)

Abstract Download Free Sample Several physiological mechanisms act to regulate renal potassium excretion and distribution. Together they comprise an integrated control system that may be envisioned as being made up of several interacting negative feedback control mechanisms, all affecting removal of potassium from the extracellular fluid by renal excretion or transfer across cell membranes into or out of the intracellular compartment. The intent of this presentation is to describe the mechanisms of potassium regulation, beginning in Chapter 1 with an overview of the system, Chapter 2 with mechanisms that determine movement of potassium between the extracellular and intracellular compartments, in Chapter 3 focusing on renal tubular transport systems, and in Chapter 4 presenting the mechanisms of control of aldosterone secretion. Greatest emphasis will be on describing the integrated functions of the components, in Chapter 5, as they operate together in a system to regulate extracellular potassium concentra...
Persistent Activation of the Fyn/ERK Kinase Signaling Axis Mediates Imatinib Resistance in Chronic Myelogenous Leukemia Cells through Upregulation of Intracellular SPARC (2010)

SPARC is an extracellular matrix protein that exerts pleiotropic effects on extracellular matrix organization, growth factor availability, cell adhesion, differentiation, and immunity in cancer. Chronic myelogenous leukemia (CML) cells resistant to the BCR-ABL inhibitor imatinib (IM-R cells) were found to overexpress SPARC mRNA. In this study, we show that imatinib triggers SPARC accumulation in a variety of tyrosine kinase inhibitor (TKI)-resistant CML cell lines. SPARC silencing in IM-R cells restored imatinib sensitivity, whereas enforced SPARC expression in imatinib-sensitive cells promoted viability as well as protection against imatinib-mediated apoptosis. Notably, we found that the protective effect of SPARC required intracellular retention inside cells. Accordingly, SPARC was not secreted into the culture medium of IM-R cells. Increased SPARC expression was intimately linked to persistent activation of the Fyn/ERK kinase signaling axis. Pharmacologic inhibition of this pathway or siRNA-mediated knockdown of Fyn kinase resensitized IM-R cells to imatinib. In support of our findings, increased levels of SPARC mRNA were documented in blood cells from CML patients after 1 year of imatinib therapy compared with initial diagnosis. Taken together, our results highlight an important role for the Fyn/ERK signaling pathway in imatinib-resistant cells that is driven by accumulation of intracellular SPARC.
Web Content Mining: A Solution To Consumer'S Product Hunt (2008)

With the rapid growth in business size, today's businesses orient towards electronic technologies. Amazon.com and e-bay.com are some of the major stakeholders in this regard. Unfortunately the enormous size and hugely unstructured data on the web, even for a single commodity, has become a cause of ambiguity for consumers. Extracting valuable information from such an everincreasing data is an extremely tedious task and is fast becoming critical towards the success of businesses. Web content mining can play a major role in solving these issues. It involves using efficient algorithmic techniques to search and retrieve the desired information from a seemingly impossible to search unstructured data on the Internet. Application of web content mining can be very encouraging in the areas of Customer Relations Modeling, billing records, logistics investigations, product cataloguing and quality management. In this paper we present a review of some very interesting, efficient yet implementable techniques from the field of web content mining and study their impact in the area specific to business user needs focusing both on the customer as well as the producer. The techniques we would be reviewing include, mining by developing a knowledge-base repository of the domain, iterative refinement of user queries for personalized search, using a graphbased approach for the development of a web-crawler and filtering information for personalized search using website captions. These techniques have been analyzed and compared on the basis of their execution time and relevance of the result they produced against a particular search.
Fastest Mixing Markov Chain on a Graph (2004)

We consider a symmetric random walk on a connected graph, where each edge is labeled with the probability of transition between the two adjacent vertices. The associated Markov chain has a uniform equilibrium distribution; the rate of convergence to this distribution, i.e., the mixing rate of the Markov chain, is determined by the second largest eigenvalue modulus (SLEM) of the transition probability matrix. In this paper we address the problem of assigning probabilities to the edges of the graph in such a way as to minimize the SLEM, i.e., the problem of finding the fastest mixing Markov chain on the graph. We show that this problem can be formulated as a convex optimization problem, which can in turn be expressed as a semidefinite program (SDP). This allows us to easily compute the (globally) fastest mixing Markov chain for any graph with a modest number of edges (say, $1000$) using standard numerical methods for SDPs. Larger problems can be solved by exploiting various types of symmetry and structure in the problem, and far larger problems (say, 100,000 edges) can be solved using a subgradient method we describe. We compare the fastest mixing Markov chain to those obtained using two commonly used heuristics: the maximum-degree method, and the Metropolis--Hastings algorithm. For many of the examples considered, the fastest mixing Markov chain is substantially faster than those obtained using these heuristic methods. We derive the Lagrange dual of the fastest mixing Markov chain problem, which gives a sophisticated method for obtaining (arbitrarily good) bounds on the optimal mixing rate, as well as the optimality conditions. Finally, we describe various extensions of the method, including a solution of the problem of finding the fastest mixing reversible Markov chain, on a fixed graph, with a given equilibrium distribution.
Role of Obesity and Fat Distribution in Non-insulin-dependent Diabetes Mellitus in Mexican Americans and Non-Hispanic Whites (1986)

Recent data have suggested that central obesity is related positively to the prevalence of non-insulin-dependent diabetes mellitus (NIDDM). We examined whether central obesity (measured by the ratio of subscapular to triceps skinfold) was predictive of NIDDM prevalence independently of overall obesity (measured by body mass index, BMI) in 1231 Mexican Americans and 939 non-Hispanic whites who participated in the San Antonio Heart Study, a population-based survey of diabetes and cardiovascular risk factors. Mexican Americans are characterized by higher rates of NIDDM, greater overall obesity, and more central body fat distribution than age-matched non-Hispanic whites. Using multiple logistic regression with age, ethnicity, BMI, and central obesity as covariates, overall obesity was positively associated with NIDDM prevalence in both sexes (P less than 0.001) but central obesity was related to NIDDM prevalence only in women. Our data suggest that the effect of centrality decreases at higher levels of centrality. While both BMI and centrality narrow the ethnic difference in NIDDM prevalence, Mexican Americans still have an increased risk of NIDDM (odds ratio = 2.33 in men and 1.80 in women), suggesting that other factors, possibly genetic, may also be important determinants of the ethnic differences in NIDDM prevalence.
Dynamic tunneling force microscopy and single electron tunneling force spectroscopy (2012)

An introduction to Scanning Probe Microscopy is given along with some basic principles in the detection of electron tunneling by Atomic Force Microscopy (AFM) using electrostatic force. Dynamic Tunneling Force Microscopy (DTFM), a new scanned probe force-detected tunneling technique, is presented and described, in which shuttling of electrons between electron trap states and a conductive AFM probe provides a means to image these trap states with subnanometer spatial resolution. The further development of Single Electron Tunneling Force Spectroscopy (SETFS) is described, providing a method to measure the energy of electronic trap states. It is used to find the energy spectrum of individual monolayer-protected gold clusters. A novel technique is presented whereby the electron trap states’ depth and energy are independently determined using SETFS. Finally, a new technique is described and explored, by which “single spin” electron spin resonance measurements can in principle be performed. The method employs the detection of magnetic resonance through spin dependent tunneling, providing a means to identify individual paramagnetic electron states in dielectric films with atomic spatial resolution. To my wife, Bryanna—my reason for everything.
FUEL ADULTERATION CONSEQUENCES IN INDIA : A REVIEW (2013)

The quantum of petroleum product utilization in India is increasing due to increase in population, urbanization, development activities and changes in life style, which leads to widespread pollution in the environment. Thus tailpipe emissions from low level public transport such as auto rickshaw is a menace and become a serious problem due to their contribution in pollution and bypassing the subsidized kerosene to adulteration market. As fuel prices rise, the public transport driver cuts costs by blending the cheaper hydrocarbon into highly taxed hydrocarbon. The blending may be as much as 80-90%. Fuel adulteration is essentially an unintended consequence of tax policies and the attempt to control fuel prices, in the name of fairness. Air pollution is the ultimate result. This problem is not unique to India, but prevalent in many developing countries including those outside of south Asia. This problem is largely absent in economies that do not regulate the ability of fuel producers to innovate or price based on market demand. In the present paper developed techniques for fuel adulteration with kerosene and resulting tailpipe emissions causing environmental impacts has been studied.