gebhart/patrepeval huggingface dataset:
Pro‐apoptotic therapy with the oligonucleotide Genasense<sup>TM</sup> (oblimersen sodium) targeting Bcl‐2 protein expression enhances the biological anti‐tumour activity of rituximab (2004)

New strategies have evolved in the treatment of patients with non-Hodgkin's lymphoma (NHL). Anti-sense oligonucleotides (ASO) and monoclonal antibody (mAb) therapy, though proven to be safe and effective, have not demonstrated to be curative when used as single agents. We tested an innovative combination strategy involving various mAbs and ASO against Bcl-2 (G3139) in aggressive preclinical models. G3139, under optimal transfection conditions, decreased the proliferation rate of lymphoma cells by 60-75% when compared with controls. In addition, apoptosis was demonstrated in Raji (25%) and DHL-4 cells (30%) treated with Genasense following downregulation of Bcl-2 protein. Downregulation of Bcl-2 by G3139 was associated with a higher degree of rituximab-associated, complement-mediated cytotoxicity and antibody dependent cellular cytotoxicity when compared with rituximab alone-treated controls. In vivo studies in severe combined immunodeficiency (SCID) mice clearly demonstrated synergistic activity between G3139 and rituximab. Treatment of lymphoma-bearing SCID mice with G3139 for two consecutive days prior to each rituximab dose resulted in better disease control and survival than treatment with either agent alone or controls. Our findings suggest that Bcl-2 downregulation by G3139, followed by the administration of rituximab is an efficient anti-tumour strategy associated with improved survival in lymphoma-bearing SCID mice.
Improving the specific synthetic activity of a penicillin g acylase using DNA family shuffling. (2003)

Penicillin G Acylas (PGA) of Providencia rettgeri (ATCC 25599) was evolved using a modified DNA family shuffling method. The identity of pga genes from Escherichia coli, Kluyvera citrophila and Providencia rettgeri ranges from 62.5% to 96.9%. The pga genes from above three species were recombined and shuffled to create interspecies pga gene fusion libraries. By substituting assembled chimaeras for corresponding region of pETPPGA, different recombinants were constructed and expressed in E. coli JM109(DE3). Mutants with obvious beta-lactam synthetic activity were selected from the plates and the ratios of synthesis to hydrolysis (S/H) were determined subsequently. It was shown that the primary structures of selected positives exhibited significant diversity among each library. The best mutant possessed 40% higher synthetic activity than the wild type enzyme of PrPGA. It was further proved in this study that the domain of alpha subunit contributed much more to improve the specific activity of synthesis. Results showed a recombinant PGA with higher synthetic activity was acquired by the method of DNA shuffling.
Prevalence of Hearing Aid Use Among Older Adults in the United States (2012)

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Building blocks of a semantic Web framework - requirements analysis and architectural implications (2004)

The Internet initially spread to all areas of business, information and communication with amazing speed. Recent enhancements to its communicative and informative effectiveness have been much slower in acceptance. This is caused by the increased complexity of these new services. No longer can new technologies (e.g. Web services and ontologies) be used by anyone (as is true for e.g. HTML). Quite to the contrast the new technologies require a deep understanding of the topics involved (e.g. agent architectures and knowledge engineering). One of the foremost tasks in the near future thus is to provide abstraction layers that facilitate the usage of these new technologies. Our WASP framework aims to simplify the access and reuse of technologies like Web services, agents and large-scale knowledge bases. This paper describes the individual building blocks, the basic requirements and the necessary infrastructure to connect the individual building blocks in more detail.
Silk (2014)

Silks are naturally spun fibrous proteins most often associated with the silkworm and spiders. Silk fibers are unusual in combining strength, toughness, and compressibility. The proteins are characterized primarily by a β-sheet secondary structure consisting of a highly crystalline region as well as regions of lower crystallinity. Silkworm cocoon fibers have been used in textiles for thousands of years. Spider silk, of which there are many different types, has not been domesticated. Water-soluble silk proteins are synthesized and stored in the silk glands until spun into fibers, at which point they become insoluble in water. The spinning process is regulated by the organism and involves the extrusion of the soluble silk in a liquid crystalline state through spinnerets. Silks are stable to approximately 230°C. Membranes have been formed from silks that provide a useful means to explore secondary structure and to entrap enzymes. Worldwide production of silkworm silk for textiles is expected to increase. Future applications depend on the success of biotechnology to provide adequate production levels of specifically tailored silk compositions.
The Design and Analysis of a Semidynamic Deterministic Routing Rule (1981)

The best deterministic rule, newly proposed in this paper is similar in nature to the best stochastic rule [3], except that 1) a maximum traffic bifurcation flow distribution is chosen and 2) deterministic routing sequences are used. Analysis shows that the best deterministic rule always gives better delay performance than the best stochastic rule. A semidynamic version of this rule is introduced for use in a varying traffic rate environment.
Complete spontaneous necrosis of hepatocellular carcinoma confirmed on resection: A case report (2016)

We present a rare case of complete spontaneous necrosis of HCC and strongly recommended surgical intervention.
Enzyme‐Responsive Multifunctional Magnetic Nanoparticles for Tumor Intracellular Drug Delivery and Imaging (2011)

Enzyme-responsive, hybrid, magnetic silica nanoparticles have been employed for multifunctional applications in selective drug delivery and intracellular tumor imaging. In this study, doxorubicin (Dox)-conjugated, enzyme-cleavable peptide precursors were covalently tethered onto the surface of uniform silica-coated magnetic nanoparticles through click chemistry. This enzyme-responsive nanoparticle conjugate demonstrated highly efficient Dox release upon specific enzyme interactions in vitro. It also exhibits multiple functions in selective tumor intracellular drug delivery and imaging in the tumor cells with high cathepsin B expression, whereas it exhibited lower cytotoxicity towards other cells without enzyme expression.
Use of site-directed mutagenesis to identify valine-573 in the S'1 binding site of rat neutral endopeptidase 24.11 (enkephalinase) (1990)

On the basis of the identity of a segment of the amino acid sequence within the active site of the bacterial enzyme thermolysin and the mammalian enzyme neutral endopeptidase 24.11, the possible involvement of valine-573 of neutral endopeptidase 24.11 in substrate binding was investigated. Valine-573 was changed to leucine and to alanine by site-directed mutagenesis. The effect of these mutations on inhibitor binding and substrate catalysis was examined with a series of compounds containing variable P'1 residues. With a small P'1 residue such as alanine, both mutant enzymes exhibited kinetic properties essentially the same as the wild-type enzyme. However, with larger P'1 residues such as phenylalanine, tyrosine, and leucine, the Val573Leu mutant showed a 24-100-fold decrease in inhibitor affinity. Similarly substrates containing bulky P'1 residues showed a 10-40-fold decrease in Vmax with little change in Km. In contrast, the Val573Ala mutant showed only modest changes in terms of inhibitor binding or substrate turnover. These results support the proposed role of valine-573 as a part of the hydrophobic binding pocket, S'1 binding subsite, of neutral endopeptidase 24.11.
Crystal Structure of Quinone Reductase 2 in Complex with Resveratrol<sup>,</sup> (2004)

Resveratrol has been shown to have chemopreventive, cardioprotective, and antiaging properties. Here, we report that resveratrol is a potent inhibitor of quinone reductase 2 (QR2) activity in vitro with a dissociation constant of 35 nM and show that it specifically binds to the deep active-site cleft of QR2 using high-resolution structural analysis. All three resveratrol hydroxyl groups form hydrogen bonds with amino acids from QR2, anchoring a flat resveratrol molecule in parallel with the isoalloxazine ring of FAD. The unique active-site pocket in QR2 could potentially bind other natural polyphenols such as flavonoids, as proven by the high affinity exhibited by quercetin toward QR2. K562 cells with QR2 expression suppressed by RNAi showed similar properties as resveratrol-treated cells in their resistance to quinone toxicity. Furthermore, the QR2 knockdown K562 cells exhibit increased antioxidant and detoxification enzyme expression and reduced proliferation rates. These observations could imply that the chemopreventive and cardioprotective properties of resveratrol are possibly the results of QR2 activity inhibition, which in turn, up-regulates the expression of cellular antioxidant enzymes and cellular resistance to oxidative stress.
Dioxo-Bridged Dinuclear Manganese(III) and -(IV) Complexes of Pyridyl Donor Tripod Ligands:  Combined Effects of Steric Substitution and Chelate Ring Size Variations on Structural, Spectroscopic, and Electrochemical Properties (2003)

The syntheses and structural, spectral, and electrochemical characterization of the dioxo-bridged dinuclear Mn(III) complexes [LMn(mo-O)(2)MnL](ClO(4))(2), of the tripodal ligands tris(6-methyl-2-pyridylmethyl)amine (L(1)) and bis(6-methyl-2-pyridylmethyl)(2-(2-pyridyl)ethyl)amine (L(2)), and the Mn(II) complex of bis(2-(2-pyridyl)ethyl)(6-methyl-2-pyridylmethyl)amine (L(3)) are described. Addition of aqueous H(2)O(2) to methanol solutions of the Mn(II) complexes of L(1) and L(2) produced green solutions in a fast reaction from which subsequently precipitated brown solids of the dioxo-bridged dinuclear complexes 1 and 2, respectively, which have the general formula [LMn(III)(mu-O)(2)Mn(III)L](ClO(4))(2). Addition of 30% aqueous H(2)O(2) to the methanol solution of the Mn(II) complex of L(3) ([Mn(II)L(3)(CH(3)CN)(H(2)O)](ClO(4))(2) (3)) showed a very sluggish change gradually precipitating an insoluble black gummy solid, but no dioxo-bridged manganese complex is produced. By contrast, the Mn(II) complex of the ligand bis(2-(2-pyridyl)ethyl)(2-pyridylmethyl)amine (L(3a)) has been reported to react with aqueous H(2)O(2) to form the dioxo-bridged Mn(III)Mn(IV) complex. In cyclic voltammetric experiments in acetonitrile solution, complex 1 shows two reversible peaks at E(1/2) = 0.87 and 1.70 V (vs Ag/AgCl) assigned to the Mn(III)(2) <--> Mn(III)Mn(IV) and the Mn(III)Mn(IV) <--> Mn(IV)(2) processes, respectively. Complex 2 also shows two reversible peaks, one at E(1/2) = 0.78 V and a second peak at E(1/2) = 1.58 V (vs Ag/AgCl) assigned to the Mn(III)(2) <--> Mn(III)Mn(IV) and Mn(III)Mn(IV) <--> Mn(IV)(2) redox processes, respectively. These potentials are the highest so far observed for the dioxo-bridged dinuclear manganese complexes of the type of tripodal ligands used here. The bulk electrolytic oxidation of complexes 1 and 2, at a controlled anodic potential of 1.98 V (vs Ag/AgCl), produced the green Mn(IV)(2) complexes that have been spectrally characterized. The Mn(II) complex of L(3) shows a quasi reversible peak at an anodic potential of E(p,a) of 1.96 V (vs Ag/AgCl) assigned to the oxidation Mn(II) to Mn(III) complex. It is about 0.17 V higher than the E(p,a) of the Mn(II) complex of L(3a). The higher oxidation potential is attributable to the steric effect of the methyl substituent at the 6-position of the pyridyl donor of L(3).
Direct numerical simulations of turbulent channel flow with transverse square bars on one wall (2003)

Direct numerical simulations have been carried out for a fully developed turbulent channel flow with a smooth upper wall and a lower wall consisting of square bars separated by a rectangular cavity. A wide range of $w/k$ , the cavity width to roughness height ratio, was considered. For $w/k\,{\ge}\,7$ , recirculation zones occur immediately upstream and downstream of each element while mean streamlines and spatial distributions of the skin frictional drag indicate that each element is virtually isolated. The maximum form drag occurs at $w/k\,{=}\,7$ and coincides with the minimum skin frictional drag. The dependence on $w/k$ of the Clauser roughness function reflects that of the form drag.
A Study of Proppant Formation Reactions (2009)

Abstract Based on long-term API conductivity data, proppants are generally chosen to optimize fracturing cost versus fracture conductivity. This long-term data is acquired by measuring conductivity for two days at simulated conditions of closure stress and reservoir temperature. It is recognized that the majority of the conductivity damage to a proppant pack occurs rapidly during the first day at simulated conditions. It is clear on examination of raw data that conductivity has not reached equilibrium after two days of flow, but rather it is still declining. Investigators who have studied the effect of longer flow-time on fracture conductivity of proppants have all concluded that the decline in conductivity continues for a much longer time. Much attention has been given to the mechanical properties of proppants to aid in the selection of the best material for a particular fracture treatment. These properties include: size, proppant-size distribution, sphericity, hardness, crush resistance, and acid solubility. Other than acid solubility, little information about the chemical reactivity of the proppants has been noted. Recent work has demonstrated that, at some reservoir conditions, certain proppants become significantly chemically reactive. This paper presents the proppant as starting material for geochemical reactions with various aqueous fluids saturated in typical formation minerals. Methods have been developed for rapid testing of these interactions, and test results clearly demonstrate how important proppant chemical reactivity is as losses in proppant-pack permeability of 50–90% were obtained, owing to the genesis of cementatious and porosity-filling minerals. In addition, some proppant chemistries were found to be much more susceptible to these types of reactions, losing much of their mechanical strength in a surprisingly short period of time. Results from this study indicate that operators who rely solely on API test methods in evaluating the suitability of proppants for particular downhole conditions might miss significant damage potential from geochemical reactions occurring between the proppant and formation fluids.
Contrast-Enhanced MRI of the Breast after Limited Surgery and Radiation Therapy (1993)

Accordingly, contrast-enhanced MR is not recommended during the first 9 months after therapy. Nine to 18 months after therapy, it may be helpful in those two-thirds of cases where the scar does not enhance. If enhancement takes place (one-third of cases), it may represent either scar or tumor, and in such circumstances, enhanced MR is of no value. After 18 months, enhanced MRI has proven a valuable additional tool. By correctly detecting or excluding recurrent tumor, it can significantly improve diagnostic accuracy.
LAG3: The Biological Processes That Motivate Targeting This Immune Checkpoint Molecule in Human Cancer (2019)

The programmed cell death 1 (PD-1) pathway is an important regulator of immune responses in peripheral tissues, including abnormal situations such as the tumor microenvironment. This pathway is currently the principal target for immunotherapeutic compounds designed to block immune checkpoint pathways, with these drugs improving clinical outcomes in a number of solid and hematological tumors. Medical oncology is experiencing an immune revolution that has scientists and clinicians looking at alternative, non-redundant inhibitory pathways also involved in regulating immune responses in cancer. A variety of targets have emerged for combinatorial approaches in immune checkpoint blockade. The main purpose of this narrative review is to summarize the biological role of lymphocyte activation gene 3 (LAG3), an emerging targetable inhibitory immune checkpoint molecule. We briefly discuss its role in infection, autoimmune disease and cancer, with a more detailed analysis of current data on LAG3 expression in breast cancer. Current clinical trials testing soluble LAG3 immunoglobulin and LAG3 antagonists are also presented in this work.
The World of Connections and Information Flow in Twitter (2012)

Information propagation in online social networks like Twitter is unique in that word-of-mouth propagation and traditional media sources coexist. We collect a large amount of data from Twitter to compare the relative roles different types of users play in information flow. Using empirical data on the spread of news about major international headlines as well as minor topics, we investigate the relative roles of three types of information spreaders: 1) mass media sources like BBC; 2) grassroots, consisting of ordinary users; and 3) evangelists, consisting of opinion leaders, politicians, celebrities, and local businesses. Mass media sources play a vital role in reaching the majority of the audience in any major topics. Evangelists, however, introduce both major and minor topics to audiences who are further away from the core of the network and would otherwise be unreachable. Grassroots users are relatively passive in helping spread the news, although they account for the 98% of the network. Our results bring insights into what contributes to rapid information propagation at different levels of topic popularity, which we believe are useful to the designers of social search and recommendation engines.
Thyristor-controlled in-phase boosting for h.v. d.c. convertors (1980)

An alternative scheme to the conventional h.v. d.c. rectifier station is proposed. The transformer on-load tap-changer and convertor controls are replaced by a thyristor-controlled regulating transformer, the rectifier bridges consisting of pure diodes. Fast and continuous voltage control is achieved with improved displacement factor and reduced harmonic content.
Statistics of Natural Images: Scaling in the Woods (1993)

In order to best understand a visual system one should attempt to characterize the natural images it processes. We gather images from the woods and find that these scenes possess an ensemble scale invariance. Further, they are highly non-Gaussian, and this non-Gaussian character cannot be removed through local linear filtering. We find that including a simple gain control nonlinearity in the filtering process makes the filter output quite Gaussian, meaning information is maximized at fixed channel variance. Finally, we use the measured power spectrum to place an upper bound on the information conveyed about natural scenes by an array of receptors.
The ground state of pluripotency (2010)

Pluripotency is defined as the capacity of individual cells to initiate all lineages of the mature organism in response to signals from the embryo or cell culture environment. A pluripotent cell has no predetermined programme; it is a blank slate. This is the foundation of mammalian development and of ES (embryonic stem) cell biology. What are the design principles of this naïve cell state? How is pluripotency acquired and maintained? Suppressing activation of ERKs (extracellular-signal-regulated kinases) is critical to establishing and sustaining ES cells. Inhibition of GSK3 (glycogen synthase kinase 3) reinforces this effect. We review the effect of selective kinase inhibitors on pluripotent cells and consider how these effects are mediated. We propose that ES cells represent a ground state, meaning a basal proliferative state that is free of epigenetic restriction and has minimal requirements for extrinsic stimuli. The stability of this state is reflected in the homogeneity of ES cell populations cultured in the presence of small-molecule inhibitors of MEK (mitogen-activated protein kinase/ERK kinase) and GSK3.
Preference for Incorporating Young Adults' Religious Beliefs into Counseling Sessions (2001)

Young adults may be particularly vulnerable to stressful experiences that might negatively impact their mental health and tap their limited coping abilities. Campus clinics provide one avenue for receiving help in times of need. However, so might prayer and religious counseling. The current study was designed to begin examining whether young adults perceive the inclusion of religious beliefs in counseling sessions as beneficial. Participants (n = 125) completed surveys on religious beliefs and practices. They also evaluated one of two scenarios depicting religious or traditional counseling sessions. Although no significant difference existed between participants who identified themselves as religious or non-religious in their assessment of the appropriateness of counseling or the need for counseling, results showed a positive association between stress susceptibility and lack of religiousness. The benefits of including religious beliefs in counseling sessions are discussed.
Management of Cranial and Spinal Infections (1998)

Department of Neurosurgery, University of Minnesota, Box 96, 520 Delaware Street, SE, Minneapolis, MN 55455
Design of knowledge-based expert systems for time-critical applications (2002)

Real-time knowledge-based systems (KBSs) are increasingly used to monitor and control real-time processes. Although a KBS may perform well on the average in terms of computation time, it may fail to deliver results while meeting deadlines in some critical cases. This is not acceptable in a hard real-time system where all timing constraints imposed by the environment must be continuously observed by the embedded computer and the failure to meet a single deadline may be catastrophic. Thus the technology for building a new generation of real-time KBSs must be developed before we can rely on these smart systems to perform complex, safety-critical monitoring and control functions in a real-time environment as we currently do on embedded software programs implemented in procedural languages. In this article, we examine some fundamental issues in the design and development of real-time KBSs including (1) response time analysis, and (2) rule-base optimization and synthesis.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>