gebhart/patrepeval huggingface dataset:
The Challenge of Targeting Notch in Hematologic Malignancies (2014)

Notch signaling can play oncogenic and tumor suppressor roles depending on cell type. Hematologic malignancies encompass a wide range of transformed cells, and consequently the roles of Notch are diverse in these diseases. For example Notch is a potent T-cell oncogene, with >50% of T-cell acute lymphoblastic leukemia (T-ALL) cases carry activating mutations in the Notch1 receptor. Targeting Notch signaling in T-ALL with gamma-secretase inhibitors, which prevent Notch receptor activation, has shown pre-clinical activity, and is under evaluation clinically. In contrast, Notch signaling inhibits acute myeloblastic leukemia growth and survival, and although targeting Notch signaling in AML with Notch activators appears to have pre-clinical activity, no Notch agonists are clinically available at this time. As such, despite accumulating evidence about the biology of Notch signaling in different hematologic cancers, which provide compelling clinical promise, we are only beginning to target this pathway clinically, either on or off. In this review, we will summarize the evidence for oncogenic and tumor suppressor roles of Notch in a wide range of leukemias and lymphomas, and describe therapeutic opportunities for now and the future.
Antidepressants Cause Lethal Disruption of Membrane Function in the Human Protozoan Parasite <i>Leishmania</i> (1984)

The antidepressant compounds clomipramine and nitroimipramine were cidal to extracellular promastigotes of both human protozoan parasites Leishmania donovani and Leishmania major. Clomipramine also killed amastigotes of both species within murine macrophages with no apparent toxicity to the host cells. Further, amastigotes were more sensitive than promastigotes to clomipramine. Clomipramine (100 micromoles per liter or 0.2 nanomole per 1 X 10(6) cells) inhibited L-proline transport in promastigotes. Synergistic inhibition of L-proline transport was observed with clomipramine after addition of either of the ionophores valinomycin or nigericin. These observations suggest that the cytotoxic effects of clomipramine result from its disruption of the proton electrochemical gradient of the parasite surface membrane.
Topology of Multivesicular Liposomes, a Model Biliquid Foam (1996)

Freeze-fracture electron microscopy was used to characterize the microstructure of a novel multivesicular liposome (MVL) currently under investigation as a depot-type drug delivery vehicle. The interior of the MVL includes bilayer-enclosed, water-filled compartments surrounded by an encapsulating outer membrane. The contacts between compartments exhibit tetrahedral coordination analogous to a gas−liquid foam that persists to the bilayer level, and the compartments take on a variety of polyhedral shapes and sizes. Close examination of the distribution of polyhedra shows that it is nearly identical to theoretical predictions and computer simulations of polytetrahedral random close packing. As such, the MVL structure is one of the first experimental visualizations of the polytetrahedral random close packed molecular structure predicted for liquids and metallic glasses.
Current Strategies of Secondary Prevention After a Cerebrovascular Event (2001)

Current recommendations are applied in clinical practice, but great variability between different centers remains. More clearly defined guidelines for indications for, as well as contraindications against, a specific therapy are necessary.
Binding and Inhibition of Copper Ions to RecA Inteins from <i>Mycobacterium tuberculosis</i> (2010)

Protein splicing is a unique post-translational process in which an intein excises itself from a precursor with the concomitant ligation of flanking sequences. The binding of zinc to intein inhibits protein splicing reversibly and EDTA relieves the inhibition. Copper was found to inhibit protein trans splicing; however, the recovery of intein splicing required both EDTA and TCEP, suggesting a different inhibition mechanism for copper compared to zinc. In this work, we have investigated the binding properties and inhibition effects of copper ions on the RecA intein from Mycobacterium tuberculosis. Both Cu(+) and Cu(2+) exhibited high binding affinity to inteins, while different binding sites were identified. Cu(2+) coordinates to Cys1, the key residue involved in the mechanism of protein splicing, however, Cu(+) does not coordinate to cysteine. An in vitro inhibition assay indicated that monovalent Cu(+) demonstrates reversible inhibition to protein splicing, and the inhibitory efficiency is comparable to Zn(2+). Redox reaction between Cu(2+) and cysteine in inteins were observed and the rate constants were determined. The results suggested a dual role for Cu(2+) in the inhibition of intein splicing: strong coordination of Cu(2+) to key residues (including Cys1) in the intein, and subsequent oxidation of Cys1, the residue required for the N-->S acyl shift step in protein splicing. A kinetic study suggested that the coordination could be the major cause of inhibition effect of Cu(2+) initially, whereas the redox reaction could play an additional role in inhibition at a later stage.
β‐Arrestin1 and β‐arrestin2 are differentially required for phosphorylation‐dependent and ‐independent internalization of δ‐opioid receptors (2005)

Beta-arrestins are key negative regulators and scaffolds of G protein-coupled receptor (GPCR) signalling. Beta-arrestin1 and beta-arrestin2 preferentially bind to the phosphorylated GPCRs in response to agonist stimulation, resulting in receptor internalization and desensitization. The critical roles of GPCR kinases (GRKs)-catalyzed receptor phosphorylation and interaction of beta-arrestins with the phosphorylated receptor in receptor internalization are well established. However, emerging evidence suggests that an agonist-stimulated internalization mechanism that is independent of receptor phosphorylation may also be employed in some cases, although the molecular mechanism for the phosphorylation-independent GPCR internalization is not clear. The current study investigated the role of receptor phosphorylation and the involvement of different beta-arrestin subtypes in agonist-induced delta-opioid receptor (DOR) internalization in HEK293 cells. Results from flow cytometry, fluorescence microscopy, and surface biotin labelling experiments showed that elimination of agonist-induced DOR phosphorylation by mutation GRK binding or phosphorylation sites only partially blocked agonist-induced receptor internalization, indicating the presence of an agonist-induced, GRK-independent mechanism for DOR internalization. Fluorescence and co-immunoprecipitation studies indicated that both the wild-type DOR and the phosphorylation-deficient mutant receptor could bind and recruit beta-arrestin1 and beta-arrestin2 to the plasma membrane in an agonist-stimulated manner. Furthermore, internalization of both the wild-type and phosphorylation-deficient receptors was increased by overexpression of either type of beta-arrestins and blocked by dominant-negative mutants of beta-arrestin-mediated internalization, demonstrating that both phosphorylation-dependent and -independent internalization require beta-arrestin. Moreover, double-stranded RNA-mediated interference experiments showed that either beta-arrestin1 or beta-arrestin2 subtype-specific RNAi only partially inhibited agonist-induced internalization of the wild-type DOR. However, agonist-induced internalization of the phosphorylation-deficient DOR was not affected by beta-arrestin1-specific RNAi but was blocked by RNAi against beta-arrestin2 subtype. These data indicate that endogenous beta-arrestin1 functions exclusively in the phosphorylation-dependent receptor internalization, whereas endogenous beta-arrestin2, but not beta-arrestin1, is required for the phosphorylation-independent receptor internalization. These results thus provide the first evidence of different requirement for beta-arrestin isoforms in the agonist induced phosphorylation-dependent and -independent GPCR internalization.
Automatic verification of concurrent object properties (2002)

The paper introduces an object-oriented modeling language based on concurrently executing and communicating objects. A logical framework to formally design object systems and prove their properties is briefly presented. This framework is based on a local and system logic which are variants of linear temporal logic. In order to prove system properties, we have developed tableau methods (with decision procedures) for both levels. Unlike other decision methods for checking satisfiability or validity, who construct the full set of all possible states of the satisfaction graph, these algorithms construct only those states reachable by the system (or object) from its initial state and satisfying the formula to be checked.
Identification of Protein Intermediates in the Processing of the p55 HIV-1 gag Precursor in Cells Infected with Recombinant Vaccinia Virus (1989)

We have used a recombinant vaccinia virus (VV) which expresses high levels of human immunodeficiency virus-1 (HIV-1) gag proteins to analyze the processing pathway of the gag p55 precursor. HIV-1 gag proteins were isolated from [3H]leucine-labeled VV:gag-infected H9 T lymphocytes by immunoprecipitation with either anti-p24, anti-p17, or anti-p6 antibodies. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that processing of the p55 precursor involves three major intermediates (p41a, p41b, and p39). The p41a and p39 proteins contain the p17 and p24 protein segments, and the p41b is comprised of p24 and p15 segments. On two-dimensional gels, each intermediate as well as the mature p24 and p17 proteins migrated as distinct species. [3H]Myristic acid labeling of the HIV-1 gag proteins revealed that in addition to p55 and p17, the p41a and p39 intermediates, but not p41b, are myristylated, confirming that myristylation occurs at the NH2 terminus before cleavage of the p55 precursor protein. We conclude that the myristylated HIV-1 gag p55 precursor is initially cleaved at random either at the p17/p24 junction or at two sites between p24 and p15 proteins, resulting in three intermediates (p41a, p41b, and p39) which are subsequently cleaved to yield mature gag proteins.
Infectious bronchitis virus interference with growth of Newcastle disease virus. I. Study of interference in chicken embryos. (1963)

HE introduction of two live viruses into a susceptible host presupposes knowledge of their relative actions and the consequent response of the host to the two agents. Under such circumstances there are three possibilities: 1) independent action of each virus, 2) interference of one virus with the other, and 3) synergism. There is disagreement among the investigators who studied the effects of IBV-NDV combination in birds. Some investigators16 believe that dual infection and subsequent immune response are possible, whereas others8 sustain the thesis of interference of one virus over the other, with consequent impaired immune response. A desire to elucidate the contrasting reports and common use of combined infectious bronchitis (IB) and Newcastle disease (ND) vaccines suggested a systematic investigation of the factors involved in dual administration of the above viruses. Also considered were the interval between inoculation of the viruses and their relative amounts since these two factors are known to be responsible for either interference or dual infection.9 It was deemed necessary to confine the initial studies to a relatively simple system, such as the embryonating chicken egg (ECE), in which the effects of the two viruses may be related directly to their invasion and growth15 without detectable antibody and immune responses as observed in birds.
OnTheRun : a location-based exercise game (2011)

Going for a run is a great way to get exercise and feel rejuvenated, but it can also get repetitive and boring. In contrast, digital games can be very engaging and addictive but traditionally force players to be physically inactive. This project is a mobile phone application that transforms a run into an immersive game by presenting a series of story-based running tasks to motivate the player. Requiring that the game be played while running constrains the design both in terms of input and output, and this system demonstrates ways to manage those constraints while still providing a compelling experience. A six person evaluation validates the concept and offers useful design feedback.
10-Gigabit iWARP Ethernet: Comparative Performance Analysis with InfiniBand and Myrinet-10G (2007)

iWARP is a set of standards enabling remote direct memory access (RDMA) over Ethernet. iWARP supporting RDMA and OS bypass, coupled with TCP/IP offload engines, can fully eliminate the host CPU involvement in an Ethernet environment. With the iWARP standard and the introduction of 10-Gigabit Ethernet, there is now an alternative path to the proprietary interconnects for high-performance computing, while maintaining compatibility with existing Ethernet infrastructure and protocols. Recently, NetEffect Inc. has introduced an iWARP-enabled 10-Gigabit Ethernet channel adapter. In this paper we assess the potential of such an interconnect for high-performance computing by comparing its performance with two leading cluster interconnects, infiniband and myrinet-10G. The results show that the NetEffect iWARP implementation achieves an unprecedented latency for Ethernet, and saturates 87% of the available bandwidth. It also scales better with multiple connections. At the MPI level, iWARP performs better than infiniband in queue usage and buffer re-use.
An Interest Shaping Mechanism in NDN: Joint Congestion Control and Traffic Management (2018)

Congestion control is one of the most critical issues in Named Data Networking (NDN). Compared to traditional Internet, NDN has some new features: receiver-driven, in-network caching, hop-by-hop forwarding, etc. These new features pose new challenges for designing congestion control mechanism. Congestion in NDN is mainly caused by Data packets, thus, shaping the transmission rate of Interest packet can regulate the returning rate of Data packet. In this paper, we propose an Interest shaping mechanism to tackle congestion in NDN by controlling Interest packet transmission rate in an optimized way. We formulate the rate allocation problem as a global optimization problem via jointly considering congestion control and traffic management. In order to achieve traffic management objective, we add an extra term in utility function to penalize over-loaded links. By applying partial dual decomposition, we solve the optimization problem with a gradient-based algorithm and we prove that gradient-based algorithm converges to optimality of optimization. Then, we present a practical implementation of this algorithm. Finally, we conduct simulation in ndnSIM to evaluate performance of the proposed mechanism by comparing with other existing methods. Simulation results show that our proposed mechanism can achieve high ratio of satisfied Interest, low delay and packet drop rate. The proposed mechanism can also achieve fairness among flows though the link utilization may not be high.
Properties and applications of air-silica microstructured optical fiber devices (2002)

Summary form only given. Air-silica microstructured fibers (ASMF) incorporate air holes within the cladding region that run along the length of the fiber (Kaiser and Astle, 1974). Recently there has been renewed interest in such fibers because the microstructured region provides extra degrees of freedom in manipulating mode propagation, which can be exploited in a range of different applications (Birks et al, 1997; Ranka et al, 2000; Eggleton et al, 2000; Chandalia et al, 2001). To date, research has primarily focused on understanding the guidance properties of fundamental modes localized in the core region, for example, bend loss, cutoff wavelength, mode field diameter, and dispersion. A broader class of applications for ASMF, which we consider in this paper, is in the design of optical components, such as grating-based filters (Eggleton et al, 2000), and novel tapered fiber devices (Chandalia et al, 2001). In these applications, core mode guidance can be associated with total internal reflection in a high-index doped region (e.g. germanium doped core). The microstructure cladding region is then exploited to manipulate the propagation of higher order cladding modes, and, in the context of tapered fiber devices, ensures a mechanically robust device that can be spliced to standard fiber with low insertion loss, enabling a dramatically efficient nonlinear process including widely tunable Raman soliton generation.
Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native α1-Adrenoceptor Subtypes (2001)

Binding affinities of serotonin (5-HT)-receptor antagonists and agonists at human recombinant alpha1-adrenoceptor subtypes (alpha1a-, alpha1b- and alpha1d-subtypes) were examined and compared with the functional affinities obtained in rat caudal artery (alpha1A-subtype), dog carotid artery (alpha1B-subtype) and rat thoracic aorta (alpha1D-subtype). Most of the 5-HT-receptor antagonists and agonists tested showed relatively high affinity to three alpha1-adrenoceptor subtypes. The highest affinity close to 1 nM was seen for NAN-190 (5-HT1A antagonist) in binding and functional studies. 5-Methylurapidil (5-HT1A agonist) and BMY7378 (5-HT1A agonist) showed, respectively, alpha1a(alpha1A)- or alpha1d(alpha1D)-subtype selectivity in both binding and functional affinities, but spiperone (5-HT2A antagonist) showed alpha1b-selectivity only in binding affinity. Functional affinity of ritanserin (5-HT2A antagonist) to the alpha1B-subtype was approximately 500-fold lower than that of affinity to the alpha1b-subtype. The present results show that many 5-HT-receptor antagonists and agonists have high affinity to alpha1-adrenoceptors, but suggest that there is deviation between their functional affinities and binding affinities for some drugs.
CENP-A: the key player behind centromere identity, propagation, and kinetochore assembly (2012)

Chromosome segregation is the one of the great problems in biology with complexities spanning from biophysics and polymer dynamics to epigenetics. Here, we summarize the current knowledge and highlight gaps in understanding of the mechanisms controlling epigenetic regulation of chromosome segregation.
Enhancement of the Illinois scan architecture for use with multiple scan inputs (2004)

Testing cost is becoming increasingly important as system-on-chip circuits continue to become more complex. In this paper, we address the issue of reducing test cost by shortening test application time and reducing the volume of data needs to be stored on a tester. The number of scan channels on a tester and/or the number of pins on an SOC are limited. We propose a method to enhance the Illinois scan architecture for use with a small number of scan-in pins. Pin reduction is achieved by connecting a single pin to several scan chains together depending on their compatibility relations. With the use of an incompatibility graph and graph colouring algorithm, the number of pins needed is minimized.
One-sided fluxes in elliptical cylinders (2001)

The paper derives expressions for the magnetization distributions that result in one-sided fluxes in infinitely long cylinders whose cross sections are confocal ellipses. It discusses their relationship to the expressions for a circular cylinder, and gives examples of the flux distributions due to specific magnetizations.
Cascaded classification with optimal candidate selection for effective place recognition (2008)

A two-stage cascaded classification approach with an optimal candidate selection scheme is proposed to recognize places using images taken by camera phones. An optimal acceptance threshold is chosen to maximize the probability of accepting more positives and rejecting more negatives at the first stage so that an optimal number of candidates are selected. The first classifier is trained using simple color and texture features. The second classifier is trained by Scale Invariant Feature Transform (SIFT). For a query image, a number of matching candidates are selected using k nearest neighbor at the first stage and passed on to the second stage for a refining classification to select the best matching result. The searching range is narrowed down dynamically at the second stage depending on the output of the first stage. Experimental results show that this method is promising by improving the recognition accuracy and reducing the computation time.
Cranial Electrotherapy Stimulation as a Treatment for Anxiety in Chemically Dependent Persons (1986)

Cranial electrotherapy stimulation (CES) is reported to be an effective treatment for anxiety, a major presenting symptom among chemically dependent patients. In this study, 40 inpatient alcohol and/or polydrug users were given CES or sham CES in a double blind design. An additional 20 patients served as normal hospital routine controls. Dependent measures of anxiety were the Profile of Mood States, the Institute for Personality and Ability Testing Anxiety Scale, and the State/Trait Anxiety Index. CES-treated patients showed significantly greater improvement on all anxiety measures than did either control group. There were no differences in response between older and younger patients, or between the primarily drug or alcohol abusers. No placebo effect was found on any of our measures. It is concluded tht CES is a clinically significant addition to the treatment regimen for this patient population.
Separation and Recovery of Nickel and Cadmium from Spent Cd—Ni Storage Batteries and Their Process Wastes (1992)

Abstract Several typical methods for the recovery and separation of cadmium and nickel from Ni- and Cd-bearing wastes are briefly described. Laboratory- and large-scale experiments were respectively developed to improve the processes for the recovery and treatment of cadmium and nickel. A high degree of purity of recovered cadmium was obtained. Yields of >95% for nickel and >99.66% for cadmium were obtained. The large-scale experimental process involves no secondary pollution, and it decreases and sometimes eliminates the disposal of spent process streams. A plant in China has established a production line based on the large-scale process, and a large number of benefits in cadmium recovery from spent alkaline Ni—Cd storage batteries and their process wastes have resulted.
Fast cell search during PN code phase acquisition using adaptive filters in AWGN environment (2003)

This paper presents a new method of acquiring the phase of the PN sequence used in CDMA systems. The new method uses an adaptive filter where the filter taps contain the results of the sum of a block of chips. These contents are then compared with similar summation of the locally generated sequence. The acquisition peak is detected by minimizing the mean square error between the received and the locally generated sequences. The analysis of the acquisition system is presented, and analytical and simulation results are compared.
A Study on the Transmission Line Transient Protection Containing Static Synchronous Compensator (2013)

This paper focuses on the transient protection of transmission line with FACTS Devices; the principle and mathematical model of static synchronous compensator (STATCOM) has been analyzed. And feasible control strategy has been proposed considering the voltage source inverter (VSI) as a core part of the FACTS components. The simulation results verify the rightness using electromagnetic transient simulation software PSCAD/EMTDC to set up electromagnetic transient model.