gebhart/patrepeval huggingface dataset:
Using a Build-and-Click Approach for Producing Structural and Functional Diversity in DNA-Targeted Hybrid Anticancer Agents (2012)

An efficient screening method was developed for functionalized DNA-targeted platinum-containing hybrid anticancer agents based on metal-mediated amine-to-nitrile addition, a form of "click" chemistry. The goal of the study was to generate platinum-acridine agents for their use as cytotoxic "warheads" in targeted and multifunctional therapies. This was achieved by introducing hydroxyl, carboxylic acid, and azide functionalities in the acridine linker moiety and by varying the nonleaving groups attached to platinum. The assay, which was based on microscale reactions between 6 platinum-nitrile complexes and 10 acridine derivatives, yielded a small library of 60 platinum-acridines. Reactions were monitored, and product mixtures were quantitatively analyzed by automated in-line high-performance liquid chromatography-electrospray mass spectrometry (LC-ESMS) analysis and subjected to cell viability screening using a nonradioactive cell proliferation assay. The new prescreening methodology proves to be a powerful tool for establishing structure-activity relationships and for identifying target compounds.
A Novel Formal Total Synthesis of Cephalotaxine (2005)

A formal total synthesis of cephalotaxine (CET), the parent structure of antileukemia Cephalotaxus alkaloids, was achieved through a novel synthesis of the pentacyclic amino enone 4 by a rapid annulation of readily available beta-(3,4-methylenedioxy)phenethylamine (2), delta-valerolactone, and bromoacetone.
Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease (2003)

SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases.
Clean vehicles as an enabler for a clean electricity grid (2018)

California has issued ambitious targets to decarbonize transportation through the deployment of electric vehicles (EVs), and to decarbonize the electricity grid through the expansion of both renewable generation and energy storage. These parallel efforts can provide an untapped synergistic opportunity for clean transportation to be an enabler for a clean electricity grid. To quantify this potential, we forecast the hourly system-wide balancing problems arising out to 2025 as more renewables are deployed and load continues to grow. We then quantify the system-wide balancing benefits from EVs modulating the charging or discharging of their batteries to mitigate renewable intermittency, without compromising the mobility needs of drivers. Our results show that with its EV deployment target and with only one-way charging control of EVs, California can achieve much of the same benefit of its Storage Mandate for mitigating renewable intermittency, but at a small fraction of the cost. Moreover, EVs provide many times these benefits if two-way charging control becomes widely available. Thus, EVs support the state's renewable integration targets while avoiding much of the tremendous capital investment of stationary storage that can instead be applied towards further deployment of clean vehicles.
Cooperation of Both TNF Receptors in Inducing Apoptosis: Involvement of the TNF Receptor-Associated Factor Binding Domain of the TNF Receptor 75 (1998)

TNF-R55 is the main receptor mediating TNF-induced cytotoxicity. However, in some cells TNF-R75 also signals cell death. In PC60 cells, the presence of both receptor types is required to induce apoptosis following either specific TNF-R55 or TNF-R75 triggering, pointing to a mechanism of receptor cooperation. In this study, we extend previous observations and show that TNF-R55 and TNF-R75 cooperation in the case of apoptosis in PC60 cells is bidirectional. We also demonstrate ligand-independent TNF-R55-mediated cooperation in TNF-R75-induced granulocyte/macrophage-CSF secretion, but not vice versa. To determine which part of the intracellular TNF-R75 sequence was responsible for the observed receptor cooperation in apoptosis, we introduced different TNF-R75 mutant constructs in PC60 cells already expressing TNF-R55. Our data indicate that an intact TNF-R-associated factors 1 and 2 (TRAF1/TRAF2)-binding domain is required for receptor cooperation. These findings suggest a role for the TRAF complex in TNF-R cooperation in the induction of cell death in PC60 cells. Nevertheless, introduction of a dominant negative (DN) TRAF2 molecule was not able to affect receptor cooperation. Remarkably, TRAF2-DN overexpression, which was found to inhibit the TNF-dependent recruitment of endogenous wild-type TRAF2 to the TNF-R75 signaling complex, could neither block TNF-R55- or TNF-R75-induced NF-kappaB activation nor granulocyte/macrophage-CSF secretion. Possibly, additional factors different from TRAF2 are involved in TNF-mediated NF-kappaB activation.
Metabolism (1993)

The chapter contains sections titled: Introduction Principles of Energy Metabolism Enzyme Catalysis Membrane Transport Metabolic Pathways Regulation and Coordination of Metabolism Further Reading
Expression of Bcl-2, Bcl-x, and Bax after T cell activation and IL-2 withdrawal (1995)

Bcl-2, bcl-x, and bax genes code for proteins that affect the susceptibility of cells to apoptosis. In general, the expression of bcl-2 or bcl-x inhibits apoptosis while bax promotes apoptosis. We examined the levels of these proteins by immunoblotting in resting and activated T cells and in thymocytes. Bcl-2 and Bax proteins vary coordinately, but Bcl-x varies independently: Bcl-2 and Bax are higher in splenic T cells than in thymocytes, and their levels increase even more after T cell activation. In contrast, Bcl-x is almost undetectable in splenic T cells but is manyfold greater in thymocytes and in activated splenic T cells. When CTLL-2 cells or activated T cells are starved of IL (IL-2), the level of Bcl-x but not Bcl-2 protein drops before the onset of apoptosis. Stable transfection of either bcl-2 or bcl-x expression plasmids promotes the survival of CTLL-2 cells in the setting of IL-2 withdrawal. Over 70 to 90% of the transfected cells remain viable at 48 h after IL-2 withdrawal when all of the control transfected cells are apoptotic. These findings suggest that a decrease in Bcl-x protein levels precedes apoptosis after IL-2 withdrawal in T cells and that transfected bcl-2 promotes survival after IL-2 withdrawal by functionally masking this drop in Bcl-x.
ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN (2013)

Mutations in the RNA binding protein fused in sarcoma/translated in liposarcoma (FUS/TLS) cause amyotrophic lateral sclerosis (ALS). Although ALS-linked mutations in FUS often lead to a cytosolic mislocalization of the protein, the pathogenic mechanisms underlying these mutations remain poorly understood. To gain insight into these mechanisms, we examined the biochemical, cell biological and functional properties of mutant FUS in neurons. Expression of different FUS mutants (R521C, R521H, P525L) in neurons caused axonal defects. A protein interaction screen performed to explain these phenotypes identified numerous FUS interactors including the spinal muscular atrophy (SMA) causing protein survival motor neuron (SMN). Biochemical experiments showed that FUS and SMN interact directly and endogenously, and that this interaction can be regulated by FUS mutations. Immunostaining revealed co-localization of mutant FUS aggregates and SMN in primary neurons. This redistribution of SMN to cytosolic FUS accumulations led to a decrease in axonal SMN. Finally, cell biological experiments showed that overexpression of SMN rescued the axonal defects induced by mutant FUS, suggesting that FUS mutations cause axonal defects through SMN. This study shows that neuronal aggregates formed by mutant FUS protein may aberrantly sequester SMN and concomitantly cause a reduction of SMN levels in the axon, leading to axonal defects. These data provide a functional link between ALS-linked FUS mutations, SMN and neuronal connectivity and support the idea that different motor neuron disorders such as SMA and ALS may be caused, in part, by defects in shared molecular pathways.
Nature of the interaction of heparin with acidic fibroblast growth factor (1993)

The binding of human acidic fibroblast growth factor (aFGF) to heparin has been analyzed by a variety of different approaches to better elucidate the nature of this protein/sulfated polysaccharide interaction. Static and dynamic light scattering as well as analytical ultracentrifugation analyses indicates that 14-15 molecules of a FGF can bind to a 16-kDa heparin chain, with approximately 10 of these bound relatively uniformly to high-affinity sites. The dissociation constants of these latter sites are estimated to be approximately 50-140 nM on the basis of surface plasmon resonance experiments in which the association and dissociation rates of aFGF interaction with immobilized heparin were measured. The size of the binding site of a FGF on heparin was also determined by heparin lyase digestion of a FGF/heparin complexes followed by isolation and characterization of protected oligosaccharides. The smallest aFGF-protected oligosaccharide comigrated with delta UA2S(1-->4)-alpha-D-GlcNp2S6S(1-->4)-alpha-L-IdoAp-2S( 1-->4)-alpha-D-GlcNp2S6S (where delta UA represents 4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid and S is sulfate). Thus, aFGF appears to bind at high density (one molecule every 4-5 polysaccharide units) and with high affinity to heparin. This potentially provides a concentrated, stabilized storage form of the growth factor that can be released for receptor-mediated cellular activation in response to the proper stimuli. It is also possible that close proximity of aFGF molecules on the highly sulfated regions of heparan chains may be involved in the induction of receptor aggregation as suggested by Ornitz et al. [Ornitz, D. M., Yayon, A., Flanagan, J. G., Svahn, C. M., Levi, E., & Leder, P. (1992) Mol. Cell. Biol. 12, 240-247].
An improved experimental determination of external photoluminescence quantum efficiency (1997)

The external photoluminescence quantum yield of, for example, thin film semiconductors can be conveniently determined using the improved integrating‐sphere method (see Figure) presented here. Spectrally resolved detection allows the excitation source and the emission to be distinguished. The method will be particularly useful for samples with small Stocks' shifts or low photoluminescence quantum yields or for highly scattering samples. Fig magnified image
Bone Marrow Stem Cell Gene Therapy of Arylsulfatase A-Deficient Mice, Using an Arylsulfatase A Mutant That Is Hypersecreted from Retrovirally Transduced Donor-Type Cells (2001)

Arylsulfatase A (ASA)-deficient mice represent an animal model for the fatal lysosomal storage disease metachromatic leukodystrophy, which is characterized by widespread intralysosomal deposition of sulfatide. Bone marrow stem cell gene therapy in mice, using a retroviral vector mediating expression of wild-type human ASA, has the potential to ameliorate the visceral pathology, but improves the prevailing brain disease and neurologic symptoms only marginally. One factor that influences the efficacy of bone marrow transplantation therapy in lysosomal storage diseases is the secretion level of the therapeutic enzyme from donor-type cells. Here we test the potential of a hypersecreted glycosylation variant of ASA. Although this mutant lacks mannose 6-phosphate residues it is taken up by cells by a mannose 6-phosphate receptor-independent pathway and causes partial metabolic correction of ASA-deficient mouse cells. Retrovirally mediated transfer of the mutant cDNA into ASA-deficient mice results in the sustained expression of the transgene. Serum levels argue for an increased secretion of the glycosylation mutant also in vivo. Tissue levels were reduced to 2% in liver and up to 40% in kidney compared with animals treated with the wild-type enzyme, indicating reduced endocytosis. Thus, the limited uptake of the variant enzyme outweighs the putative advantageous effect of improved supply. Although the mutant enzyme is able to correct the metabolic defect partially, histological examinations did not reveal any reduction of sulfatide storage in treated animals. Surprisingly, analysis of neurologic symptoms indicated a significant improvement of the gait pattern.
Miscellaneous alkaloids: Amaryllidaceae, Sceletium, muscarine, imidazole, oxazole, peptide and other miscellaneous alkaloids (1999)

J. R. Lewis, Nat. Prod. Rep., 1999, 16, 389 DOI: 10.1039/A802500B
On the impact of concurrent downloads (2001)

Concurrent downloads accelerate information access speed for individual web users. The speed-up comes from multiple connections launched for one subject download, which leads to unfairness at user level. In this paper, we study the impact of concurrent downloads on the network. Particularly, we investigate the fairness between users who employ different downloading concurrency. We also discuss how concurrent downloads affect the transient behavior of the network.
Optimization of High-Speed DNA Sequencing on Microfabricated Capillary Electrophoresis Channels (1998)

DNA sequencing separations have been performed in microfabricated electrophoresis channels with the goal of determining whether high-quality sequencing is feasible with these microdevices. The separation matrix, separation temperature, channel length and depth, injector size, and injection parameters were optimized. DNA fragment sizing separations demonstrated that 50-micron-deep channels provide the best sensitivity for our detection configuration. One-color sequencing separations of single-stranded M13mp18 DNA on 3% linear polyacrylamide (LPA) were used to optimize the twin-T injector size, injection conditions, and temperature. The best one-color separations were observed with a 250-micron twin-T injector, an injection time of 60 s, and a temperature of 35 degrees C. The first 500 bases appeared in 9.2 min with a resolution of > 0.5, and the separation extended to 700 bases. The best four-color sequencing separations were performed using 4% LPA, a temperature of 40 degrees C, and a 100-micron twin-T injector. These four-color runs were complete in only 20 min, could be automatically base-called using BaseFinder to over 600 bp after the primer, and were 99.4% accurate to 500 bp. These results significantly advance the quality of microchip-based electrophoretic sequencing and indicate the feasibility of performing high-speed genomic sequencing with microfabricated electrophoretic devices.
Crystal Structure of the Open Form of Dog Gastric Lipase in Complex with a Phosphonate Inhibitor (2002)

Fat digestion in humans and some mammals such as dogs requires the successive intervention of two lipases: gastric lipase, which is stable and active despite the highly acidic stomach environment, followed by the classical pancreatic lipase secreted into the duodenum. We previously solved the structure of recombinant human gastric lipase (HGL) at 3.0-A resolution in its closed form; this was the first structure to be described within the mammalian acid lipase family. Here we report on the open structure of the recombinant dog gastric lipase (r-DGL) at 2.7-A resolution in complex with the undecyl-butyl (C11Y4) phosphonate inhibitor. HGL and r-DGL show 85.7% amino acid sequence identity, which makes it relevant to compare the forms from two different species. The open r-DGL structure confirms the previous description of the HGL catalytic triad (Ser(153), His(353), and Asp(324)) with the catalytic serine buried and an oxyanion hole (NH groups of Gln(154) and Leu(67)). In r-DGL, the binding of the C11Y4 phosphonate inhibitor induces part of the cap domain, the lid, to roll over the enzyme surface and to expose a catalytic crevice measuring approximately 20 x 20 x 7 A(3). The C11Y4 phosphonate fits into this crevice, and a molecule of beta-octyl glucoside fills up the crevice. The C11Y4 phosphonate inhibitor and the detergent molecule suggest a possible binding mode for the natural substrates, the triglyceride molecules.
JET VAPOR DEPOSITION™: AN ALTERNATIVE TO ELECTRODEPOSITION (1995)

Electrodeposition is widely used to deposit a variety of metals and alloys. Although high rates can be achievedusing this technique, there is limited control over the microstructure of the deposits and in many instances the use of toxic precursors and disposal of toxic effluents has to be considered. This has spurred the development of alternative deposition processes. The Jet Vapor Deposition™ (JVD™) process is a rapidly emerging ‘green’ technology which allows control of microstructure at high deposition rates. A brief discussionof the principles of JVD and representative applications in the deposition of metals (such as copper and gold) and alloys (Cu–Ag and Ag–Sn) are presented.
Bandits with unobserved confounders: a causal approach (2015)

The Multi-Armed Bandit problem constitutes an archetypal setting for sequential decision-making, permeating multiple domains including engineering, business, and medicine. One of the hallmarks of a bandit setting is the agent's capacity to explore its environment through active intervention, which contrasts with the ability to collect passive data by estimating associational relationships between actions and payouts. The existence of unobserved confounders, namely unmeasured variables affecting both the action and the outcome variables, implies that these two data-collection modes will in general not coincide. In this paper, we show that formalizing this distinction has conceptual and algorithmic implications to the bandit setting. The current generation of bandit algorithms implicitly try to maximize rewards based on estimation of the experimental distribution, which we show is not always the best strategy to pursue. Indeed, to achieve low regret in certain realistic classes of bandit problems (namely, in the face of unobserved confounders), both experimental and observational quantities are required by the rational agent. After this realization, we propose an optimization metric (employing both experimental and observational distributions) that bandit agents should pursue, and illustrate its benefits over traditional algorithms.
Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia (2008)

Frontotemporal dementia (FTD) is characterized by cognitive and behavioral changes and, in a significant subset of patients, Parkinsonism. Histopathologically, FTD frequently presents with tau-containing lesions, which in familial cases result from mutations in the MAPT gene encoding tau. Here we present a novel transgenic mouse strain (K3) that expresses human tau carrying the FTD mutation K369I. K3 mice develop a progressive histopathology that is reminiscent of that in human FTD with the K369I mutation. In addition, K3 mice show early-onset memory impairment and amyotrophy in the absence of overt neurodegeneration. Different from our previously generated tau transgenic strains, the K3 mice express the transgene in the substantia nigra (SN) and show an early-onset motor phenotype that reproduces Parkinsonism with tremor, bradykinesia, abnormal gait, and postural instability. Interestingly, motor performance of young, but not old, K3 mice improves upon L-dopa treatment, which bears similarities to Parkinsonism in FTD. The early-onset symptoms in the K3 mice are mechanistically related to selectively impaired anterograde axonal transport of distinct cargos, which precedes the loss of dopaminergic SN neurons that occurs in aged mice. The impaired axonal transport in SN neurons affects, among others, vesicles containing the dopamine-synthesizing enzyme tyrosine hydroxylase. Distinct modes of transport are also impaired in sciatic nerves, which may explain amyotrophy. Together, the K3 mice are a unique model of FTD-associated Parkinsonism, with pathomechanistic implications for the human pathologic process.
Deep Learning with Differential Privacy (2016)

Machine learning techniques based on neural networks are achieving remarkable results in a wide variety of domains. Often, the training of models requires large, representative datasets, which may be crowdsourced and contain sensitive information. The models should not expose private information in these datasets. Addressing this goal, we develop new algorithmic techniques for learning and a refined analysis of privacy costs within the framework of differential privacy. Our implementation and experiments demonstrate that we can train deep neural networks with non-convex objectives, under a modest privacy budget, and at a manageable cost in software complexity, training efficiency, and model quality.
Distributed Access Control with Blockchain (2019)

The specification and enforcement of network-wide policies in a single administrative domain is common in today's networks and considered as already resolved. However, this is not the case for multi-administrative domains, e.g. among different enterprises. In such situation, new problems arise that challenge classical solutions such as PKIs, which suffer from scalability and granularity concerns. In this paper, we present an extension to Group-Based Policy -a widely used network policy languagefor the aforementioned scenario. To do so, we take advantage of a permissioned blockchain implementation (Hyperledger Fabric) to distribute access control policies in a secure and auditable manner, preserving at the same time the independence of each organization. Network administrators specify polices that are rendered into blockchain transactions. A LISP control plane (RFC 6830) allows routers performing the access control to query the blockchain for authorizations. We have implemented an end-to-end experimental prototype and evaluated it in terms of scalability and network latency.
Soluble Perfluoropolymers (1998)

Soluble perfluoropolymers, readily coatable as thin films, have recently appeared on the market for premium applications such as for pellicles and fiber optic coatings. These polymers (e.g., Teflon AF and Cytop) are inherently expensive because of multistep monomer preparations, for example, of perfluorodimethyldioxole in the case of Teflon AF. Here the authors report how less expensive monomers can be used to achieve similar solubility, coatability, and optical properties. These novel polymers also have a significantly lower glass transition temperature as compared to Teflon AF and Cytop.
Neutralizing antibodies in Borna disease virus-infected rats (1995)

Borna disease is a neurologic syndrome caused by infection with a nonsegmented, negative-strand RNA virus, Borna disease virus. Infected animals have antibodies to two soluble viral proteins, p40 and p23, and a membrane-associated viral glycoprotein, gp18. We examined the time course for the development of neutralization activity and the expression of antibodies to individual viral proteins in sera of infected rats. The appearance of neutralizing activity correlated with the development of immunoreactivity to gp18, but not p40 or p23. Monospecific and monoclonal antibodies to native gp18 and recombinant nonglycosylated gp18 were also found to have neutralizing activity and to immunoprecipitate viral particles or subparticles. These findings suggest that gp18 is likely to be present on the surface of the viral particles and is likely to contain epitopes important for virus neutralization.
A SAXS STUDY OF SILICA AEROGELS (1989)

X-ray small angle scattering (SAXS) and transmission electron microscopy (TEM) are used to characterise the fractal properties of base catalysed silical aerogels : observation of change over points in the X-rays scattering curves confirms the existence of structural units, like building blocks or beads forming the network. The fractal behavior exists only in the beads or building blocks.