gebhart/patrepeval huggingface dataset:
Metabolic Biomarkers of Ageing in C57BL/6J Wild-Type and Flavin-Containing Monooxygenase 5 (FMO5)-Knockout Mice (2018)

It was recently demonstrated in mice that knockout of the flavin-containing monooxygenase 5 gene, <i>Fmo5</i>, slows metabolic ageing via pleiotropic effects. We have now used an NMR-based metabonomics approach to study the effects of ageing directly on the metabolic profiles of urine and plasma from male, wild-type C57BL/6J and <i>Fmo5</i><sup>-/-</sup> (FMO5 KO) mice back-crossed onto the C57BL/6J background. The aim of this study was to identify metabolic signatures that are associated with ageing in both these mouse lines and to characterize the age-related differences in the metabolite profiles between the FMO5 KO mice and their wild-type counterparts at equivalent time points. We identified a range of age-related biomarkers in both urine and plasma. Some metabolites, including urinary 6-hydroxy-6-methylheptan-3-one (6H6MH3O), a mouse sex pheromone, showed similar patterns of changes with age, regardless of genetic background. Others, however, were altered only in the FMO5 KO, or only in the wild-type mice, indicating the impact of genetic modifications on mouse ageing. Elevated concentrations of urinary taurine represent a distinctive, ageing-related change observed only in wild-type mice.
Human tissue kallikrein in the treatment of acute ischemic stroke (2019)

Acute ischemic stroke (AIS) remains a major cause of death and disability throughout the world. The most severe form of stroke results from large vessel occlusion of the major branches of the Circle of Willis. The treatment strategies currently available in western countries for large vessel occlusion involve rapid restoration of blood flow through removal of the offending blood clot using mechanical or pharmacological means (e.g. tissue plasma activator; tPA). This review assesses prospects for a novel pharmacological approach to enhance the availability of the natural enzyme tissue kallikrein (KLK1), an important regulator of local blood flow. KLK1 is responsible for the generation of kinins (bradykinin and kallidin), which promote local vasodilation and long-term vascularization. Moreover, KLK1 has been used clinically as a direct treatment for multiple diseases associated with impaired local blood flow including AIS. A form of human KLK1 isolated from human urine is approved in the People's Republic of China for subacute treatment of AIS. Here we review the rationale for using KLK1 as an additional pharmacological treatment for AIS by providing the biochemical mechanism as well as the human clinical data that support this approach.
Non-intrusive, parallel recovery of replicated data (2003)

The increasingly widespread use of cluster architectures has resulted in many new application scenarios for data replication. While data replication is, in principle, a well understood problem. recovery of replicated systems has not yet received enough attention. In the case of clusters, recovery procedures are particularly important since they have to keep a high level of availability even during recovery. In fact, recovery is part of the normal operations of any cluster as the cluster is expected to continue working while sites leave or join the system. However, traditional recovery techniques usually require stopping processing. Once a quiescent state has been reached, the system proceeds to synchronize the state of failed or new replicas. In this paper. we concentrate on how to perform recovery in a replication middleware without having to stop processing. The proposed protocol focuses on how to minimize the redundancies that take place during concurrent recovery of several sites.
Table S4 from Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction (2023)

&lt;p&gt;sgRNA and sequencing primers used&lt;/p&gt;
Current status and future prospect of immersion lithography (2006)

Immersion lithography is rapidly approaching the manufacturing phase. A production-quality exposure tool system with NA=1.07 (Nikon NSR-S609B) was constructed to target the start of immersion lithography for IC manufacturing in 2006. Its projection optics have very small wavefront aberration and lowest local flare levels. The overlay issue has been analyzed, and its cause was found to be evaporation cooling. With the tandem stage and local fill nozzle implemented in the S609B, we have successfully avoided the evaporation cooling so that the good wet-to-dry mix-and-match overlay data have been obtained. The major part of immersion specific defects is caused by dried water-droplets, i.e. water-marks. The local fill nozzle has eliminated this defectivity by avoiding air flow in the nozzle. In the future, water immersion with NA=1.30 optics will be used for half-pitch 45nm manufacturing. Finer pattern imaging down to 32nm seems to need high-index material immersion or nonlinear double patterning, but these have several issues and concerns to be solved.
Uncovering specificity of endogenous TAU aggregation in a human iPSC-neuron TAU seeding model (2021)

Tau pathobiology has emerged as a key component underlying Alzheimer's disease (AD) progression; however, human neuronal <i>in vitro</i> models have struggled to recapitulate tau phenomena observed <i>in vivo</i>. Here, we aimed to define the minimal requirements to achieve endogenous tau aggregation in functional neurons utilizing human induced pluripotent stem cell (hiPSC) technology. Optimized hiPSC-derived cortical neurons seeded with AD brain-derived competent tau species or recombinant tau fibrils displayed increases in insoluble, endogenous tau aggregates. Importantly, <i>MAPT-</i>wild type and <i>MAPT-</i>mutant hiPSC-neurons exhibited unique propensities for aggregation dependent on the seed strain rather than the repeat domain identity, suggesting that successful templating of the recipient tau may be driven by the unique conformation of the seed. The <i>in vitro</i> model presented here represents the first successful demonstration of combining human neurons, endogenous tau expression, and AD brain-derived competent tau species, offering a more physiologically relevant platform to study tau pathobiology.
Prioritized shaping of models for solving DEC-POMDPs (2012)

An interesting class of multi-agent POMDP planning problems can be solved by having agents iteratively solve individual POMDPs, find interactions with other individual plans, shape their transition and reward functions to encourage good interactions and discourage bad ones and then recompute a new plan. D-TREMOR showed that this approach can allow distributed planning for hundreds of agents. However, the quality and speed of the planning process depends on the prioritization scheme used. Lower priority agents shape their models with respect to the models of higher priority agents. In this paper, we introduce a new prioritization scheme that is guaranteed to converge and is empirically better, in terms of solution quality and planning time, than the existing prioritization scheme for some problems.
Chemically resolved solid state NMR images of polymers (1994)

Abstract Polymers are generally spatially heterogeneous, either in terms of morphology or as blends of various components. Solid state NMR imaging provides a means of characterizing both the chemical/morphological composition and its spatial variation. Here we discuss multiple‐pulse line‐narrowing approaches to acquiring high resolution NMR images and how these sequences can be modified so as to be sensitive to the chemical composition of a sample.
Exploitation of agricultural by-products for the recovery of bioactive compounds with applications in cosmetic industry (2015)

The agricultural, food and forestry industries produce large amounts of by-products that are considered wastes. However, recent studies have shown that these by-products contain bioactive compounds with several applications in industry.
Dynamic versus Static Optimization Techniques for Object‐Oriented Languages (1995)

Object‐oriented programs can be optimized either dynamically, i.e., based on run‐time information, or statically, i.e., based on program analysis alone. Two promising optimization techniques for object‐oriented languages are type feedback (dynamic) and concrete type inference (static). We directly compare the two techniques, evaluating their effectiveness on a suite of 23 S elf programs while keeping other factors constant. Our results show that both systems inline &gt;95% of all sends and deliver similar overall performance with one exception: S elf ' s automatic coercion of machine integers to arbitrary‐precision integers upon overflow confounds type inference and slows down arithmetic‐intensive benchmarks. We also show that a system combining the two optimizations can combine their strengths and outperform each individual optimization. We discuss several other issues which, given the comparable run‐time performance, may influence the choice between type feedback and type inference.
3R regeneration of a 40-Gbit/s optical signal by optical parametric amplification in a highly-nonlinear fiber (2005)

We demonstrate wavelength-shift-free 3R-regeneration of 40-Gbit/s optical RZ signal by OPA with a clock-modulated pump in highly-nonlinear fiber. The power penalty is improved by 2.6 dB, and the signal power is amplified by 7 dB.
A novel agonist of CD137 immune checkpoint stimulator serves as a cancer immunoprevention agent with efficacy against various tumor types (2019)

Abstract Background CD137 immune checkpoint stimulator plays an important role in T cell responses and has been targeted for cancer immunotherapy using agonistic Abs with shown toxicity. We herein report that a novel oligomeric form of the CD137 ligand, SA-4-1BBL, as a single agent has robust cancer immunoprevention efficacy against various tumors in mice without detectable toxicity, whereas an agonistic Ab to CD137 did not protect mice against tumor challenge. Study Design Mice (C57BL/6 or BALB/c) were pretreated s.c. with SA-4-1BBL protein or an agonistic Ab (3H3) to CD137 and subsequently challenged s.c. at various times (0 to 12 weeks) with different tumor cell lines. SA-4- 1BBL-treated mice without tumor challenge were euthanized 7 days later to harvest lymphoid tissues for immunophenotyping. Results Pretreatment with SA-4-1BBL protected mice against 4 different tumor types; 3LL lung, TC-1 cervical, B16-F10 melanoma, and A20 lymphoma. The conferred protection against tumors was dose-dependent and evolved within two weeks of SA-4-1BBL pretreatment and lasted for &amp;gt; 8 weeks. In marked contrast, pretreatment with the agonistic Ab had no impact on the tumor growth. CD4+CD44+CD137+ T cells and NK cells producing IFN- γ were expanded by SA-4-1BBL. Depletion of CD4+ T and NK cells or blockade of IFN-γ totally abrogated the protective effect. Depletion of CD8+ T or B cells had no significant impact on tumor growth. Importantly, SA-4- 1BBL as a single agent also prevented post-surgical tumor recurrences. Conclusion This study demonstrates that SA-4-1BBL is a novel CD137 agonist with desired features for cancer immunoprevention and immunotherapy.
Structural Characterization of Baxter's Recombinant Human ADAMTS13 Drug Candidate. (2012)

Abstract Abstract 2236 Baxter has developed a human recombinant (r) ADAMTS13 for treatment of patients with hereditary TTP. The protein is produced in a CHO cell-line using serum and protein-free fermentation technology. The purification process does not use immune-affinity chromatography, and includes two viral reduction steps. The final drug product is formulated without proteins of animal or human origin. Here we characterize preclinical and clinical lots of rADAMTS13 with respect to their structural properties. The molecular weight of rADAMTS13 was determined by MALDI TOF as ∼173 kDa. SDS-PAGE showed one band at ∼190 kDa; no additional distinct protein bands corresponding to other proteins or product related degradation products were visible in the gels. Investigation of the primary structure of rADAMTS13 by peptide mapping revealed a sequence coverage of 98% compared to the theoretical amino acid sequence, and no peptides from the signal or propeptide. Peptide mapping was also used to determine posttranslational modifications of rADAMTS13. Seven O-glycosylation sites were identified in addition to the predicted N-glycosylation, O-fucosylation and C-mannosylation sites. The relative monosaccharide and N-linked oligosaccharides composition was consistent in all preclinical and clinical rADAMTS13 batches. The main N-glycan structure found on rADAMTS13 is a biantennary, core fucosylated complex type oligosaccharide with one or two sialic acids. Quantification of sialic acid determination showed consistent amounts of sialic acid on the terminal ends of the glycans in preclinical and clinical rADAMTS13 samples. N-glycolylneuraminic acid, a potentially immunogenic variant of sialic acid, was &lt;1% the amount of total sialic acids. Higher order structure analysis using dynamic light scattering showed a similar hydrodynamic diameter for all preclinical and clinical lots. Finally, FT-IR and CD analysis showed comparable amounts of α-helix and β-sheet in preclinical and clinical lots. Taken together, similarity was shown between the preclinical and clinical lots of rADAMTS13 in all assays. A phase I clinical trial using rADAMTS13 for the treatment of hereditary TTP patients is expected to start soon. Disclosures: Foettinger-Vacha: Baxter Innovations GmbH: Employment. Kaliwoda:Baxter Innovations GmbH: Employment. Matthiessen:Baxter Innovations GmbH: Employment. Hasslacher:Baxter Innovations GmbH: Employment. Rottensteiner:Baxter Innovations GmbH: Employment. Turecek:Baxter Innovations GmbH: Employment. Mitterer:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.
Magnetically defined domain isolation for studies of nucleation and growth coercivities (2005)

Magnetic domain nucleation site distributions within a perpendicular magnetic film were measured by magnetically confining nucleated domains within small regions in the film. The confinement was achieved by placing a high coercivity layer adjacent to the layer under test and using the stray fields from domains recorded in this layer to magnetostatically halt domain wall motion in the test layer. Experimental results confirm the functionality of this method, and are shown for two samples with different magnetic properties.
Teaching performance testing (2021)

Performance testing plays a vital role in the verification of large scale software systems. It is used for testing the speed, responsiveness, capacity and stability of the investigated system. However, despite the significance of this topic, the effort invested in teaching performance testing in Computer Science is insufficient. The current paper shows, how the fundamentals of performance testing can be demonstrated to students both from a theoretical and a practical viewpoint through step-by-step practical examples that are used in the industry. It is also discussed how a basic toolchain can be set up for performance tests using only free tools. With the presented examples, the reader will be able to take first steps in the performance testing area.&#x0D; Subject Classification: 68M15
Mathematical and Structural Characterization of Strong Nonadditive Structure–Activity Relationship Caused by Protein Conformational Changes (2018)

In medicinal chemistry, accurate prediction of additivity-based structure-activity relationship (SAR) analysis rests on three assumptions: (1) a consistent binding pose of the central scaffold, (2) no interaction between the R group substituents, and (3) a relatively rigid binding pocket in which the R group substituents act independently. Previously, examples of nonadditive SAR have been documented in systems that deviate from the first two assumptions. Local protein structural change upon ligand binding, through induced fit or conformational selection, although a well-known phenomenon that invalidates the third assumption, has not been linked to nonadditive SAR conclusively. Here, for the first time, we present clear structural evidence that the formation of a hydrophobic pocket upon ligand binding in PDE2 catalytic site reduces the size of another distinct subpocket and contributes to strong nonadditive SAR between two otherwise distant R groups.
Switch Peptides: pH‐Induced α‐Helix to β‐Sheet Transitions of Bis‐amphiphilic Oligopeptides (1991)

The interconversion of two secondary structure types (α‐helix ⇆ β‐sheet) induced by external conditions such as pH, temperature, concentration, and solvent could be proved in a new class of amphiphilic peptides (switch peptides) in aqueous solution. The pH‐dependent conformational changes were studied by CD spectroscopy. Special attention was given to the investigations of four newly synthesized peptides with similar sequences.
The inter-relationships between ovarian-independent growth, tumorigenicity, invasiveness and antioestrogen resistance in the malignant progression of human breast cancer (1989)

Among the processes contributing to the progressive acquisition of the highly malignant phenotype in breast cancer are ovarian-independent growth, antioestrogen resistance and increased metastatic potential. We have previously observed that increased invasiveness and development of ovarian-independent growth occur independently. In an attempt to define the inter-relationships between these processes further, we have compared the phenotypes of ovarian-independent, invasive and antioestrogen-resistant sublines of the ovarian-dependent human breast cancer cell line MCF-7. Cells acquiring ovarian-independent growth can retain sensitivity to anti-oestrogens. One clone of MCF-7 cells selected for stable antioestrogen resistance has become non-tumorigenic but its invasive potential remains unaltered. Thus, acquisitions of some characteristics of the progressed phenotype can occur independently. This phenomenon of independent parameters in phenotypic progression could partly explain the considerable intra- and intertumour heterogeneity characteristic of breast tumours.
Blue Emitting Phosphors for Projection Cathode Ray Tubes: and (1988)

Substitution of yttrium or gadolinium for lanthanum in leads to efficient blue‐emitting and phosphors. Energy efficiencies under cathode ray excitation of 11% have been realized for phosphors with emission colors comparable with that of . The optimum preparation procedure consists in firing cerium‐activated oxalates in a flowing atmosphere containing bromine at 1100°C. Thermal quenching and linearity of the luminescence have been investigated. The hygroscopicity should pose no problems in screen manufacturing. Application of and especially could lead to a significant increase in the brightness of projection television systems.
Full-field exposure tools for ArF immersion lithography (2006)

Immersion lithography has by far satisfied most expectations regarding its feasibility as the next lithographic technique for the 65-nm node and below. To further advance 193-nm immersion lithography, a means of efficiently controlling water as an immersion fluid and research and development concerning resist processes are necessary. In 2004, Nikon Corporation introduced a 0.85 numerical aperture (NA) 193-nm immersion exposure tool that uses water as the immersion liquid. This engineering evaluation tool (EET) is equipped with a highly efficient temperaturestabilized water nozzle assembly. Selete Inc. in collaboration with Nikon Corporation has been evaluating the performance and various characteristics of the EET while also investigating various photoresist and topcoat processes. We selected three types of standard immersion processes that offered the best performance for our evaluation purposes. A resolution limit of 70-nm half-pitch line-and-space (L/S) patterns has been confirmed. A 0.8-&#956;m depth of focus (DOF) was also verified for an 80-nm half-pitch L/S pattern. In addition, full wafer (WF) critical dimension (CD) uniformity of less than 5 nm (3 sigma) has been demonstrated for a 90-nm half-pitch L/S pattern on a 300-mm wafer (WF). After the implementation of various improvements to both the EET and the topcoat/resist processes, we have achieved a total defect density of 0.23/cm<sup>2</sup>, and this defect level is low enough for pilot production.
Disambiguation Techniques for Freehand Object Manipulations in Virtual Reality (2020)

Manipulating virtual objects using bare hands has been an attractive interaction paradigm in virtual and augmented reality due to its intuitive nature. However, one limitation of freehand input lies in the ambiguous resulting effect of the interaction. The same gesture performed on a virtual object could invoke different operations on the object depending on the context, object properties, and user intention. We present an experimental analysis of a set of disambiguation techniques in a virtual reality environment, comparing three input modalities (head gaze, speech, and foot tap) paired with three different timings in which options appear to resolve ambiguity (before, during, and after an interaction). The results indicate that using head gaze for disambiguation during an interaction with the object achieved the best performance.
Fast Light and the Speed of Information Transfer in the Presence of Detector Noise (2009)

The phenomenon of fast-light pulse propagation has seen renewed interest in recent years, but its relationship to the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">speed of information transfer</i> is still being debated. In this paper, we define the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">speed of information transfer</i> as the propagation speed of a point of constant signal-to-noise ratio (SNR) on the leading edge of a signal pulse. We use standard telecommunication analysis to include the effects of noise so that the bit-error rate (BER) can be calculated as a function of a variable decision time. We introduce the concept of a time-dependent Q-factor so that pulse arrival times can be compared at equivalent BERs. We show that when receiver noise is included in a gain-assisted fast-light system, the measured <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">speed of information transfer</i> can exceed the speed of light for an equivalent pulse travelling through a vacuum.