gebhart/patrepeval huggingface dataset:
SV40 intron, a potent strong intron element that effectively increases transgene expression in transfected Chinese hamster ovary cells (2018)

Chinese hamster ovary (CHO) cells have become the most widely utilized mammalian cell line for the production of recombinant proteins. However, the product yield and transgene instability need to be further increased and solved. In this study, we investigated the effect of five different introns on transgene expression in CHO cells. hCMV intron A, adenovirus tripartite leader sequence intron, SV40 intron, Chinese hamster EF-1alpha gene intron 1 and intervening sequence intron were cloned downstream of the eGFP expression cassette in a eukaryotic vector, which was then transfected into CHO cells. qRT-PCR and flow cytometry were used to explore eGFP expression levels. And gene copy number was also detected by qPCR, respectively. Furthermore, the erythropoietin (EPO) protein was used to test the selected more strong intron. The results showed that SV40 intron exhibited the highest transgene expression level among the five compared intron elements under transient and stable transfections. In addition, the SV40 intron element can increase the ratio of positive colonies and decrease the coefficient of variation in transgene expression level. Moreover, the transgene expression level was not related to the gene copy number in stable transfected CHO cells. Also, the SV40 intron induced higher level of EPO expression than IVS intron in transfected CHO cell. In conclusion, SV40 intron is a potent strong intron element that increases transgene expression, which can readily be used to more efficient transgenic protein production in CHO cells.
Amelioration of behavioural toxicity of aluminium by oligomeric silicic acid and humic acid (2001)

Despite its limited solubility at neutral pH, aluminium is significantly accumulated by the freshwater snail Lymnaea stagnalis, leading to behavioral toxicity. Both organic (humic acid) and non-organic (oligomeric silicic acid) ligands have been shown to reduce Al accumulation probably owing to their binding affinity for Al. This study examined the effect of these ligands on behavioral responses to Al over a 30-day exposure period. Both behavioral state score (a measure of general activity) and feeding behaviors were initially (days 2-4) depressed in the presence of 500 µgl -1 added Al, followed by apparent tolerance (days 8-16) and subsequent depression (day 30). In the presence of either oligomeric Si (molar ratio Al:Si 1:40) or humic acid (10 mgl -1 ) behavioral responses to Al were completely abolished. Neither ligand alone had any effect on behavior except for a slight increase in biting activity in the presence of humic acid on days 2 -4. These results suggest that the presence of complexing ligands may affect toxicity of Al in the natural environment at neutral pH.
Managing Process Model Complexity via Concrete Syntax Modifications (2011)

While Business Process Management (BPM) is an established discipline, the increased adoption of BPM technology in recent years has introduced new challenges. One challenge concerns dealing with the ever-growing complexity of business process models. Mechanisms for dealing with this complexity can be classified into two categories: 1) those that are solely concerned with the visual representation of the model and 2) those that change its inner structure. While significant attention is paid to the latter category in the BPM literature, this paper focuses on the former category. It presents a collection of patterns that generalize and conceptualize various existing mechanisms to change the visual representation of a process model. Next, it provides a detailed analysis of the degree of support for these patterns in a number of state-of-the-art languages and tools. This paper concludes with the results of a usability evaluation of the patterns conducted with BPM practitioners.
Accurate Sequence Analysis of a Monoclonal Antibody by Top-Down and Middle-Down Orbitrap Mass Spectrometry Applying Multiple Ion Activation Techniques (2018)

Targeted top-down (TD) and middle-down (MD) mass spectrometry (MS) offer reduced sample manipulation during protein analysis, limiting the risk of introducing artifactual modifications to better capture sequence information on the proteoforms present. This provides some advantages when characterizing biotherapeutic molecules such as monoclonal antibodies, particularly for the class of biosimilars. Here, we describe the results obtained analyzing a monoclonal IgG1, either in its ∼150 kDa intact form or after highly specific digestions yielding ∼25 and ∼50 kDa subunits, using an Orbitrap mass spectrometer on a liquid chromatography (LC) time scale with fragmentation from ion-photon, ion-ion, and ion-neutral interactions. Ultraviolet photodissociation (UVPD) used a new 213 nm solid-state laser. Alternatively, we applied high-capacity electron-transfer dissociation (ETD HD), alone or in combination with higher energy collisional dissociation (EThcD). Notably, we verify the degree of complementarity of these ion activation methods, with the combination of 213 nm UVPD and ETD HD producing a new record sequence coverage of ∼40% for TD MS experiments. The addition of EThcD for the >25 kDa products from MD strategies generated up to 90% of complete sequence information in six LC runs. Importantly, we determined an optimal signal-to-noise threshold for fragment ion deconvolution to suppress false positives yet maximize sequence coverage and implemented a systematic validation of this process using the new software TDValidator. This rigorous data analysis should elevate confidence for assignment of dense MS<sup>2</sup> spectra and represents a purposeful step toward the application of TD and MD MS for deep sequencing of monoclonal antibodies.
Distribution and Apparent Spread ofEntomophaga maimaiga(Zygomycetes: Entomophthorales) in Gypsy Moth (Lepidoptera: Lymantriidae) Populations in North America (1991)

Journal Article Distribution and Apparent Spread of Entomophaga maimaiga (Zygomycetes: Entomophthorales) in Gypsy Moth (Lepidoptera: Lymantriidae) Populations in North America Get access J. S. Elkinton, J. S. Elkinton 1 Department of Entomology, University of Massachusetts, Amherst, Mass. 01003 Search for other works by this author on: Oxford Academic PubMed Google Scholar A. E. Hajek, A. E. Hajek 2 Boyce Thompson Institute, Tower Rd., Ithaca, N.Y. 14853-1801 Search for other works by this author on: Oxford Academic PubMed Google Scholar G. H. Boettner, G. H. Boettner 1 Department of Entomology, University of Massachusetts, Amherst, Mass. 01003 Search for other works by this author on: Oxford Academic PubMed Google Scholar E. E. Simons E. E. Simons 3 Department of Environmental Resources, Commonwealth of Pennsylvania, 34 Airport Drive, Middletown, Pa. 17057 Search for other works by this author on: Oxford Academic PubMed Google Scholar Environmental Entomology, Volume 20, Issue 6, 1 December 1991, Pages 1601–1605, https://doi.org/10.1093/ee/20.6.1601 Published: 01 December 1991 Article history Received: 26 April 1991 Accepted: 12 August 1991 Published: 01 December 1991
Chaos Has Come Again (1998)

Under normal circumstances, fluctuations in a laser's output power or frequency would be cause for concern. But such fluctuations may be a manifestation of deterministic chaos, which can be harnessed for communication at high data rates. In his research commentary, Gauthier discusses work published in the same issue by [VanWiggeren and Roy][1] in which an erbium-doped ring laser was used to produce chaotic light, into which a message was embedded and later recovered. The results demonstrated the feasibility of private, high-bandwidth optical communication with chaotic systems.

 [1]: http://www.sciencemag.org/cgi/content/short/279/5354/1198
The Metabotropic Glutamate Receptor Subtype 7 rs3792452 Polymorphism Is Associated with the Response to Methylphenidate in Children with Attention-Deficit/Hyperactivity Disorder (2014)

The present study suggests that the GRM7 rs37952452 polymorphism may play a role in the treatment response to methylphenidate in children with ADHD. Further studies to evaluate the association between glutamate genes and treatment response to methylphenidate in children with ADHD, including a replication of our findings using a control or comparative group in a larger sample, are warranted.
Droplet Mixer based on Siphon-Induced Flow Discretization and Phase Shifting (2009)

We present a novel mixing principle for centrifugal microfluidic platforms. Siphon structures are designed to disrupt continuous flows in a controlled manner into a sequence of discrete droplets, displaying individual volumes as low as 60 nL. When discrete volumes of different liquids are alternately issued into a common reservoir, a striation pattern of alternating liquid layers is obtained. In this manner diffusion distances are drastically decreased and a fast and homogeneous mixing is achieved. Efficient mixing is demonstrated for a range of liquid combinations of varying fluid properties such as aqueous inks or saline solutions and human plasma. Volumes of 5 muL have been mixed in less than 20 s to a high mixing quality. One-step dilutions of plasma in a standard phosphate buffer solution up to 1:5 are also demonstrated.
Speed-Dependent Treadmill Training in Ambulatory Hemiparetic Stroke Patients (2002)

Background and Purpose — A new gait training strategy for patients with stroke seeks to increase walking speed through treadmill training. This study compares the effects of structured speed-dependent treadmill training (STT) (with the use of an interval paradigm to increase the treadmill speed stepwise according to principles of sport physiology) with limited progressive treadmill training (LTT) and conventional gait training (CGT) on clinical outcome measures for patients with hemiparesis. Methods — Sixty ambulatory poststroke patients were each randomly selected to receive 1 of the 3 different gait therapies: 20 subjects were treated with STT, 20 subjects were trained to walk on a treadmill with a 20% increase of belt speed over the treatment period (LTT), and 20 subjects were treated with CGT. Treatment outcomes were assessed on the basis of overground walking speed, cadence, stride length, and Functional Ambulation Category scores. Results — After a 4-week training period, the STT group scored significantly higher than the LTT and CGT groups for overground walking speed (STT versus LTT, P <0.001; STT versus CGT, P <0.001), cadence (STT versus LTT, P =0.007; STT versus CGT, P <0.001), stride length (STT versus LTT, P <0.001; STT versus CGT, P <0.001), and Functional Ambulation Category scores (STT versus LTT, P =0.007; STT versus CGT, P <0.001). Conclusions — Structured STT in poststroke patients resulted in better walking abilities than LTT or CGT. This gait training strategy provides a dynamic and integrative approach for the treatment of gait dysfunction after stroke.
High-resolution modeling of moving and deforming objects using sparse geometric and dense photometric measurements (2010)

Modeling moving and deforming objects requires capturing as much information as possible during a very short time. When using off-the-shelf hardware, this often hinders the resolution and accuracy of the acquired model. Our key observation is that in as little as four frames both sparse surface-positional measurements and dense surface-orientation measurements can be acquired using a combination of structured light and photometric stereo, resulting in high-resolution models of moving and deforming objects. Our system projects alternating geometric and photometric patterns onto the object using a set of three projectors and captures the object using a synchronized camera. Small motion among temporally close frames is compensated by estimating the optical flow of images captured under the uniform illumination of the photometric light. Then spatial-temporal photogeometric reconstructions are performed to obtain dense and accurate point samples with a sampling resolution equal to that of the camera. Temporal coherence is also enforced. We demonstrate our system by successfully modeling several moving and deforming real-world objects.
Overexpression of<i>OsMYC2</i>Results in the Up-Regulation of Early JA-Rresponsive Genes and Bacterial Blight Resistance in Rice (2016)

JASMONATE ZIM-domain (JAZ) proteins act as transcriptional repressors of jasmonic acid (JA) responses and play a crucial role in the regulation of host immunity in plants. Here, we report that OsMYC2, a JAZ-interacting transcription factor in rice (Oryza sativa L.), plays an important role in the resistance response against rice bacterial blight, which is one of the most serious diseases in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo). The results showed that OsMYC2 interacted with some OsJAZ proteins in a JAZ-interacting domain (JID)-dependent manner. The up-regulation of OsMYC2 in response to JA was regulated by OsJAZ8. Transgenic rice plants overexpressing OsMYC2 exhibited a JA-hypersensitive phenotype and were more resistant to Xoo. A large-scale microarray analysis revealed that OsMYC2 up-regulated OsJAZ10 as well as many other defense-related genes. OsMYC2 selectively bound to the G-box-like motif of the OsJAZ10 promoter in vivo and regulated the expression of early JA-responsive genes, but not of late JA-responsive genes. The nuclear localization of OsMYC2 depended on a nuclear localization signal within JID. Overall, we conclude that OsMYC2 acts as a positive regulator of early JA signals in the JA-induced resistance against Xoo in rice.
Demonstration of two distinct transferrin receptor recycling pathways and transferrin-independent receptor internalization in K562 cells. (1986)

The endocytosis and recycling of the human transferrin receptor were evaluated by several experimental modalities in K562 cells perturbed with 10(-5) M monensin. The work presented is an extension of a previous study demonstrating both complete inhibition of release of internalized human transferrin and a 50% reduction in the number of cell surface transferrin binding sites in K562 cells treated with monensin (Stein, B. S., Bensch, K. G., and Sussman, H. H. (1984) J. Biol. Chem. 259, 14762-14772). The data directly reveal the existence of two distinct transferrin receptor recycling pathways. One pathway is monensin-sensitive and is felt to represent recycling of transferrin receptors through the Golgi apparatus, and the other pathway is monensin-resistant and most likely represents non-Golgi-mediated transferrin receptor recycling. A transferrin-free K562 cell culture system was developed and used to demonstrate that cell surface transferrin receptors can be endocytosed without antecedent ligand binding, indicating that there are factors other than transferrin binding which regulate receptor internalization. Evidence is presented suggesting that two transferrin receptor recycling pathways are also operant in K562 cells under ligand-free conditions, signifying that trafficking of receptor into either recycling pathway is not highly ligand-dependent.
NADP-Malate Dehydrogenase from Unicellular Green Alga <i>Chlamydomonas reinhardtii</i>. A First Step toward Redox Regulation? (2004)

The determinants of the thioredoxin (TRX)-dependent redox regulation of the chloroplastic NADP-malate dehydrogenase (NADP-MDH) from the eukaryotic green alga Chlamydomonas reinhardtii have been investigated using site-directed mutagenesis. The results indicate that a single C-terminal disulfide is responsible for this regulation. The redox midpoint potential of this disulfide is less negative than that of the higher plant enzyme. The regulation is of an all-or-nothing type, lacking the fine-tuning provided by the second N-terminal disulfide found only in NADP-MDH from higher plants. The decreased stability of specific cysteine/alanine mutants is consistent with the presence of a structural disulfide formed by two cysteine residues that are not involved in regulation of activity. Measurements of the ability of C. reinhardtii thioredoxin f (TRX f) to activate wild-type and site-directed mutants of sorghum (Sorghum vulgare) NADP-MDH suggest that the algal TRX f has a redox midpoint potential that is less negative than most those of higher plant TRXs f. These results are discussed from an evolutionary point of view.
Strategien für den Gesundheitsmarkt – Kongress Klinikmarketing 2011 (2012)

Eine Erfolgsgeschichte: Dynamisch steigende Beteiligung in den letzten Jahren, allein von 2010 auf 2011 einen Zuwachs von 60 % und damit de facto einen Anstieg von 350 auf 561 Teilnehmerinnen und Teilnehmer verzeichnet der Kongress Klinikmarketing, der vom 21. bis 25. November 2011 in Köln stattfand.
Fluorescence Polarization-Based Rapid Detection System for Salivary Biomarkers Using Modified DNA Aptamers Containing Base-Appended Bases (2019)

The field of care testing toward the analysis of blood and saliva lacks nowadays simple test techniques for biomarkers. In this study, we have developed a novel nucleobase analog, U<sup>gu</sup>, which is a uracil derivative bearing a guanine base at the 5-position. Moreover, we attempted the development of aptamers that can bind to secretory immunoglobulin A (SIgA), which has been examined as a stress marker in human saliva. It was observed that the acquired aptamer binds strongly and selectively to the SIgA dimer (<i>K</i><sub>d</sub> = 13.6 nM) without binding to the IgG and IgA monomers of human serum. Reduction of the aptamer length (41 mer) successfully improved 4-fold the binding affinity (<i>K</i><sub>d</sub> = 3.7 nM), compared to the original, longer aptamer (78 mer). Furthermore, the development of a simple detection system for human saliva samples by fluorescence polarization was investigated, using the reported human salivary α-amylase (sAA) and the SIgA-binding aptamer. Comparison of the present method with conventional enzyme-linked immunosorbent assay techniques highlighted a significant Pearson's correlation of 0.94 and 0.83 when targeting sAA and SIgA, respectively. It is thus strongly suggested that a new simple test of stress markers in human saliva can be quantified quickly without bound/free (B/F) separation.
Nature of Glycine and Its α-Carbon Radical in Aqueous Solution: A Theoretical Investigation (2008)

Quantum chemistry calculations and classical molecular dynamics simulations have been used to examine the equilibria in solution between the neutral and zwitterionic forms of glycine and also of the glycyl radical. The established preference (by 30 kJ mol(-1)) for the zwitterion of glycine was confirmed by both the quantum chemical calculations and the classical molecular dynamics simulations. The best agreement with experiment was derived from thermodynamic integration calculations of explicitly solvated systems, which gives a free energy difference of 36.6 ± 0.6 kJ mol(-1). In contrast, for the glycyl radical in solution, the neutral form is preferred, with a calculated free energy difference of 54.8 ± 0.6 kJ mol(-1). A detailed analysis of the microsolvation environments of each species was carried out by evaluating radial distribution functions and hydrogen bonding patterns. This analysis provides evidence that the change in preference between glycine and glycyl radical is due to the inherent gas-phase stability of the neutral α-carbon radical rather than to any significant difference in the solvation behavior of the constituent species.
Radioprotection of <i>IDH1</i> -Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198 (2015)

Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. In this study, we present evidence that small-molecule inhibitors of IDH1(R132H) that are being developed for cancer therapy may pose risks with coadministration of radiotherapy. Cancer cells heterozygous for the IDH1(R132H) mutation exhibited less IDH-mediated production of NADPH, such that after exposure to ionizing radiation (IR), there were higher levels of reactive oxygen species, DNA double-strand breaks, and cell death compared with IDH1 wild-type cells. These effects were reversed by the IDH1(R132H) inhibitor AGI-5198. Exposure of IDH1 wild-type cells to D-2-hydroxyglutarate was sufficient to reduce IDH-mediated NADPH production and increase IR sensitivity. Mechanistic investigations revealed that the radiosensitivity of heterozygous cells was independent of the well-described DNA hypermethylation phenotype in IDH1-mutated cancers. Thus, our results argue that altered oxidative stress responses are a plausible mechanism to understand the radiosensitivity of IDH1-mutated cancer cells. Further, they offer an explanation for the relatively longer survival of patients with IDH1-mutated tumors, and they imply that administration of IDH1(R132H) inhibitors in these patients may limit irradiation efficacy in this setting.
Detection and Localization of Network Black Holes (2007)

Internet backbone networks are under constant flux, struggling to keep up with increasing demand. The pace of technology change often outstrips the deployment of associated fault monitoring capabilities that are built into today's IP protocols and routers. Moreover, some of these new technologies cross networking layers, raising the potential for unanticipated interactions and service disruptions that the built-in monitoring systems cannot detect. In such instances, failures may cause data packets to be silently dropped inside the network without triggering any alarms or responses (e.g., the failure is not routed around). So-called "silent failures" or "black holes" represent a critical threat to today's rapidly evolving networks. In this paper, we present a simple and effective method to detect and diagnose such silent failures. Our method uses active measurement between edge routers to raise alarms whenever end-to-end connectivity is disrupted, regardless of the cause. These alarms feed localization agents that employ spatial correlation techniques to isolate the root-cause of failure. Using data from two real systems deployed on sections of a tier-I ISP network, we successfully detect and localize three known black holes. Further, we present simulation results demonstrating that our system accurately and precisely (both greater than 80% according to our metrics) localizes a variety of failures classes.
Massively Parallel Functional Analysis of BRCA1 RING Domain Variants (2015)

Interpreting variants of uncertain significance (VUS) is a central challenge in medical genetics. One approach is to experimentally measure the functional consequences of VUS, but to date this approach has been post hoc and low throughput. Here we use massively parallel assays to measure the effects of nearly 2000 missense substitutions in the RING domain of BRCA1 on its E3 ubiquitin ligase activity and its binding to the BARD1 RING domain. From the resulting scores, we generate a model to predict the capacities of full-length BRCA1 variants to support homology-directed DNA repair, the essential role of BRCA1 in tumor suppression, and show that it outperforms widely used biological-effect prediction algorithms. We envision that massively parallel functional assays may facilitate the prospective interpretation of variants observed in clinical sequencing.