gebhart/patrepeval huggingface dataset:
Analysis of Tissue Plasminogen Activator Specificity Using Peptidyl Fluorogenic Substrates (1997)

A series of 54 fluorogenic substrates have been synthesized and evaluated for tissue-type plasminogen activator (tPA) hydrolysis in an attempt to create efficient sensitive substrates for tPA and to investigate substrate structure-efficiency correlations. All substrates contain the 6-amino-1-naphthalenesulfonamide (ANSN) leaving group, Arg in the P1 position, various amino acids in the P2 and P3 positions, and various substituents in the sulfonamide moiety of the leaving group (P' position). The majority of substrates have relatively low K(M) values (< 100 microM), reaching as low as 2.6 microM, and reasonably high k(cat) values (up to 3.6 s(-1)). These substrates have higher affinity, higher hydrolysis rates, and higher efficiency for two-chain tPA than for the single-chain form of this enzyme. Analysis of the P3 structure influence on substrate efficiency demonstrates that compounds which contain D-isomers of N-blocked bulky amino acids, such as Phe, Leu, and Val, in this position are more efficient for tPA than substrates with N-unblocked small amino acids (Ser or Pro) in the P3 position. The second-order rate constants and k(cat) values for substrate hydrolysis increase with decreases in the P2 amino acid hydrophobicity in the following manner: Leu < Val and Gly < Ser < Pro. Substrates which contain an ANSN leaving group had a higher affinity for tPA than substrates with p-nitroaniline or 7-amino-4-methylcoumarin leaving groups. Analyses of substrate hydrolysis dependence on the substrate P' structure show that the k(cat) and the second-order rate constants increased with an increase in the size of monoalkyl substituent in the sulfonamide moiety, whereas substrates which contain either glycine methyl ester or a dialkyl group displayed the lowest efficiency for tPA. The substrate Boc-(p-F)Phe-Pro-Arg-ANSNHC2H5 allowed quantitation of tPA at a concentration as low as 1 pM, a concentration significantly lower than the plasma concentration of this protein. Evaluation of the activation of single-chain tPA by factor Xa demonstrates that prothrombinase is approximately 3-fold more efficient in activating sc-tPA than factor Xa alone, increasing the initial rate of activation from 0.0055 nM/s per 1 nM of factor Xa to 0.017 nM/s per 1 nM.
Measurement of G with Angular Acceleration Feedback Method (2018)

The large spread in recent published G values suggests that there may be some undiscovered systematic sources in these experiments. With the aim of identifying possible errors and obtaining a more reliable G value, our group has performed two independent methods simultaneously. Besides the time-of-swing method which we have worked on for more than 20 years [1], [2], another determination of G with the angular acceleration feedback method was carried out at the same laboratory. In the AAF method, two coaxial turntables are used to rotate the torsion pendulum and the source masses individually. With the help of a feedback control system [3], the torsion fiber does not twist by matching the rotating rate of the two turntables. As a result, this method is insensitive to the fiber's properties. In this work, several sources of uncertainty existed in our preliminary experiment [4] are reduced: (1) An ultra-low thermal expansion (ULE) glass shelfis used to support the source masses instead of the aluminium shelf to reduce the temperature influence on the distance between source masses; (2) The background gravity gradient of the rotating shelf is measured and compensated with small blocks so that its effect to the G value is reduced to ~1 ppm; (3) Two different methods are used to check the source mass distance to improve the confidence level. With the improvements shown above and a lot of careful systematic error evaluation, a new G value with a prospective uncertainty of less than 15 ppm will be obtained.
Molecular Genetic Characteristics of FANCI, a Proposed New Ovarian Cancer Predisposing Gene (2023)

<i>FANCI</i> was recently identified as a new candidate ovarian cancer (OC)-predisposing gene from the genetic analysis of carriers of <i>FANCI</i> c.1813C>T; p.L605F in OC families. Here, we aimed to investigate the molecular genetic characteristics of <i>FANCI,</i> as they have not been described in the context of cancer. We first investigated the germline genetic landscape of two sisters with OC from the discovery <i>FANCI</i> c.1813C>T; p.L605F family (F1528) to re-affirm the plausibility of this candidate. As we did not find other conclusive candidates, we then performed a candidate gene approach to identify other candidate variants in genes involved in the FANCI protein interactome in OC families negative for pathogenic variants in <i>BRCA1</i>, <i>BRCA2</i>, <i>BRIP1</i>, <i>RAD51C</i>, <i>RAD51D</i>, and <i>FANCI</i>, which identified four candidate variants. We then investigated <i>FANCI</i> in high-grade serous ovarian carcinoma (HGSC) from <i>FANCI</i> c.1813C>T carriers and found evidence of loss of the wild-type allele in tumour DNA from some of these cases. The somatic genetic landscape of OC tumours from <i>FANCI</i> c.1813C>T carriers was investigated for mutations in selected genes, copy number alterations, and mutational signatures, which determined that the profiles of tumours from carriers were characteristic of features exhibited by HGSC cases. As other OC-predisposing genes such as <i>BRCA1</i> and <i>BRCA2</i> are known to increase the risk of other cancers including breast cancer, we investigated the carrier frequency of germline <i>FANCI</i> c.1813C>T in various cancer types and found overall more carriers among cancer cases compared to cancer-free controls (<i>p</i> = 0.007). In these different tumour types, we also identified a spectrum of somatic variants in <i>FANCI</i> that were not restricted to any specific region within the gene. Collectively, these findings expand on the characteristics described for OC cases carrying <i>FANCI</i> c.1813C>T; p.L605F and suggest the possible involvement of <i>FANCI</i> in other cancer types at the germline and/or somatic level.
Effect of Water Hydrogen Bonding on the Solvent-Mediated “Oscillatory” Repulsion of C60 Fullerenes in Water (2015)

The solvent-mediated interaction of C60 fullerenes in liquid water is examined by using the combination of the probabilistic hydrogen bond model with the density functional theory. This combination allows one to take into account the effect of hydrogen bonding between water molecules on their interaction with fullerenes and to construct an approximation for the distribution of water molecules in the system, which provides an efficient foundation for studying hydrophobic phenomena. Our numerical evaluations predict the solvent-induced interaction of two C60 fullerenes in water at 293 K to have an oscillatory-repulsive character (previously observed in molecular dynamics simulations) only when the vicinal water-water hydrogen bonds are slightly weaker than bulk ones. Besides indicating the direction of the energetic alteration of water-water hydrogen bonds near C60 fullerenes, our model also suggests that the hydrogen bonding ability of water plays a defining role in the solvent-mediated C60-C60 repulsion.
CD38 Chimeric Antigen Receptor Engineered T Cells As Therapeutic Tools for Multiple Myeloma (2014)

Abstract Chimeric Antigen Receptors (CARs) are engineered constructs consisting of an antibody-derived antigen recognition domain linked to intracellular T cell signaling domains. Cytotoxic T cells transduced to express tumor-reactive CARs are highly promising tools for immunotherapy of cancer. The CD38 molecule, with its high and homogenous expression on Multiple Myeloma (MM) tumor cells, is considered a suitable target for antibody therapy of MM. Prompted by this, we evaluated the feasibility and efficacy of targeting MM cells with CD38-CAR-transduced T cells (CD38-CAR T cells). To this end, we generated three different retroviral CAR constructs based on human CD38 antibodies as antigen recognition domain, CD3zeta and 41BB (CD137) as signaling domains and transduced them into PBMCs of a healthy donor. After in vitro selection and expansion, all CD38-CAR T cells, either unsorted or CD4/CD8 sorted, effectively lysed MM cell lines in a dose-, and CD38 expression-dependent manner, with a better efficacy for the CD8+ fraction. CD38-CAR T cells also effectively eradicated primary MM cells in the bone marrow mononuclear cells derived from MM patients, indicating their clinical relevancy. Although CD38-CAR T cells also displayed cytotoxic activity against the CD38+ fraction of mature monocytes and NK cells and to a lesser extent CD38+ B and T cells, they did not affect the outgrowth of CD34+ cells into various myeloid lineages. In addition,CD38-CAR T cell activity was effectively controllable by transducing them with a caspase 9-based inducible suicide gene. More interestingly, we discovered that the CD38-CAR T cells were themselves devoid of CD38 surface expression, indicating that CD38 was not essential for T cell expansion and function. Finally, in a novel in vivo xenotransplant model (UM9 cell line), in which myeloma cells were grown in a humanized bone marrow microenvironment, i.v. as well as intra tumor administration of CD38-CAR T cells established significant anti-tumor effects, proving that CD38-CAR endowed cytotoxic T lymphocytes, even with no CD38 expression, can efficiently migrate, infiltrate and eliminate human MM tumors growing in their natural niche. These results demonstrate the feasibility and potency of CAR mediated targeting of CD38+ MM cells. Optimization of CD38-CAR and suicide-gene control of CD38 CAR T cellsmay provide next steps towards safe clinical implementation of CD38-CAR T cell immune therapy. Disclosures Drent: Genmab BV: Guest employee (unpaid) Other. Lammerts van Bueren:Genmab : Employment. Parren:Genmab: Employment, Equity Ownership. van de Donk:Genmab BV: Research Funding; J&amp;J: Research Funding; Celgene: Research Funding. Martens:Genmab BV: Research Funding; J&amp;J: Research Funding; Celgene: Research Funding. Lokhorst:Celgene: Research Funding; J&amp;J: Research Funding; Genmab: Research Funding. Mutis:Celgene: Research Funding; J&amp;J: Research Funding; Genmab BV: Research Funding.
AANAT1 functions in astrocytes to regulate sleep homeostasis (2019)

Summary Characteristic features of sleep are conserved among species [1], and from humans to insects sleep is influenced by neural circuits involving monoamines such as serotonin and dopamine [2]. Glial cells have been increasingly implicated in mechanisms of baseline and homeostatic sleep regulation in mammals and flies [3–11], but it remains unknown whether and how glia might influence monoaminergic control of sleep. Sleep is regulated by circadian rhythms and a homeostatic drive to compensate for prolonged wakefulness, and growing evidence suggests that neural mechanisms controlling homeostatic sleep can be discriminated from those controlling baseline sleep [12–15]. In Drosophila , mutants of arylalkylamine N-acetyltransferase 1 ( AANAT1 lo ) have normal baseline amounts of sleep and motor activity, but increased rebound sleep following deprivation [16]. AANAT1 can acetylate and inactivate monoamines in vitro [17], but the role of AANAT1 in vivo remains poorly understood. We find AANAT1 to be expressed in astrocytes and subsets of neurons in the adult Drosophila brain, with levels in astrocytes declining markedly overnight. In sleep-deprived AANAT1 mutant flies, heightened rebound sleep is accompanied by increased serotonin and dopamine levels in the brain. In neurons, AANAT1 functions to limit the quantity and consolidation of nighttime sleep, but in astrocytes AANAT1 constrains the amount of rebound sleep that flies take in response to sleep deprivation. These findings distinguish sleep-control functions of AANAT1 in neurons and astrocytes, and identify a critical role for astrocytes in the regulation of monoamine bioavailability and calibration of the response to sleep need. Highlights The monoamine catabolic enzyme arylalkylamine N-acetyltransferase 1 (AANAT1) is expressed by astrocytes and subsets of serotonergic, glutamatergic, GABAergic and cholinergic neurons in the adult brain of Drosophila . AANAT1 limits accumulation of serotonin and dopamine in the brain upon sleep deprivation. Loss of AANAT1 from astrocytes, but not from neurons, causes flies to increase their daytime rebound sleep in response to overnight sleep deprivation.
Quantifying the Effect of Initialization Errors for Enabling Accurate Online Drivetrain Simulations (2019)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Simulations conducted on-board in a vehicle control module can offer valuable information to control strategies. Continued improvements to on-board computing hardware make online simulations of complex dynamic systems such as drivetrains within reach. This capability enables predictions of the system response to various control actions and disturbances. Implementation of online simulations requires model initialization that is consistent with the physical drivetrain state. However, sensor signals and estimated variables are susceptible to errors, compromising the accuracy of the initialization and any future state predictions as the simulation proceeds through the numerical integration process. This paper describes a drivetrain modeling and analysis method that accounts for initialization errors, thereby enabling accurate simulations of system behaviors. First, the hybrid dynamical system paradigm is employed to develop a torsional drivetrain model that captures the dynamics during a gear shift. The model is constructed in an analytical form and linearized to enable online mathematical analysis. Then a methodology is introduced to quantify the effect of initialization errors online. Finally, a procedure to systematically account for initialization errors is discussed. The outcome of this study demonstrates the capability for enabling accurate online simulations in the presence of sensor and state estimation errors in drivetrain applications and beyond.&lt;/div&gt;&lt;/div&gt;
Implementing kilo-instruction multiprocessors (2005)

Multiprocessors are coming into wide-spread use in many application areas, yet there are a number of challenges to achieving a good tradeoff between complexity and performance. For example, while implementing memory coherence and consistency is essential for correctness, efficient implementation of critical sections and synchronization points is desirable for performance. The multi-checkpointing mechanisms of Kilo-Instruction Processors can be leveraged to achieve good complexity-effective multiprocessor designs. We describe how to implement a Kilo-Instruction Multiprocessor that transparently, i.e. without any software support, uses transaction-based memory updates. Our model not only simplifies memory coherence and consistency hardware, but at the same time, it provides the potential for implementing high performance speculative mechanisms for commonly occurring synchronization constructs.
Origin of Poor Cyclability in Li2MnSiO4 from First-Principles Calculations: Layer Exfoliation and Unstable Cycled Structure (2014)

Good cyclability is essential for the potential application of cathode materials. Here, we investigate the structural stability of two-dimensional (2D) Li-layered and three-dimensional (3D) structured polymorphs of Li2FeSiO4 and Li2MnSiO4 using the density functional theory calculations. We find that all 2D Li-layered polymorphs of both materials are unstable upon full delithiation owing to layer exfoliation, which can lead to an amorphous structure. However, in contrast to the fact that the amorphization of Li2FeSiO4 can be prevented by the formation of the 3D cycled structure that is energetically stable, the 3D cycled structure of Li2MnSiO4 is found to be unstable during delithiationlithiation cycling. As a result, Li2MnSiO4 easily undergoes amorphization and shows a poor cyclability.
Architecture, implementation, and testing of a multiple-shell gas injection system for high current implosions on the Z accelerator (2013)

Tests are ongoing to conduct ~20 MA z-pinch implosions on the Z accelerator at Sandia National Laboratory using Ar, Kr, and D2 gas puffs as the imploding loads. The relatively high cost of operations on a machine of this scale imposes stringent requirements on the functionality, reliability, and safety of gas puff hardware. Here we describe the development of a prototype gas puff system including the multiple-shell nozzles, electromagnetic drivers for each nozzle's valve, a UV pre-ionizer, and an inductive isolator to isolate the ~2.4 MV machine voltage pulse present at the gas load from the necessary electrical and fluid connections made to the puff system from outside the Z vacuum chamber. This paper shows how the assembly couples to the overall Z system and presents data taken to validate the functionality of the overall system.
Low-complexity MMSE turbo equalization: a possible solution for EDGE (2005)

This paper deals with a low complexity receiver scheme where equalization and channel decoding are jointly optimized in an iterative process. We derive the theoretical transfer function of the infinite length linear minimum mean square error (MMSE) equalizer with a priori information. A practical implementation is exposed which employs the fast Fourier transform (FFT) to compute the equalizer coefficients, resulting in a low-complexity receiver structure. The performance of the proposed scheme is investigated for the enhanced general packet radio service (EGPRS) radio link. Simulation results show that significant power gains may be achieved with only a few (3-4) iterations. These results demonstrate that MMSE turbo equalization is an attractive candidate for single-carrier broadband wireless transmissions in long delay-spread environments.
Distal radial fractures: Percutaneous pinning with casting versus cast immobilization(Update to March 2004 report) (2008)

来自五项随机或半随机对照研究的证据表明,桡骨远端骨折常优先采用经皮穿针合并石膏固定治疗而非单纯的石膏固定,但是在大多数的临床试验中发现,两种治疗方法的效果并无统计学差异.在解剖测量和功能评分方面,经皮穿针固定(除Kapandlii穿针外)与石膏固定的效果相近或较之更好,并且并发症的发生率更低.采用Kapandii穿针技术时,在功能评分方面与石膏固定效果相当,但是桡侧缩短畸形更为严重,而且桡神经浅支的损伤也更为常见.这些结果并不代表最终的结论,根据标准指引进一步开展严格的临床试验将会更有利。
Rapid synthesis of ZnO nano-rods by one-step, room-temperature, solid-state reaction and their gas-sensing properties (2006)

ZnO nano-rods are prepared by one-step solid-state reaction of zinc acetate dihydrate, sodium hydroxide and cetyltrimethylammonium bromide (CTAB) at room temperature. The samples are characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The gas-sensing properties of the prepared material have been investigated. The results indicate that the as-prepared ZnO nano-rods are uniform with diameters of 10–30 nm and lengths of about 150–250 nm. The relatively high sensor signal and stability of sensors made from ZnO nano-rods demonstrate the potential for developing a new class of sensitive sensors.
A case of chickenpox with multiple bacterial complications requiring surgical treatment (2022)

Chickenpox is a controlled infection, even a single vaccination effectively prevents the development of severe forms (up to 98%). Purpose — to demonstrate a case of severe chicken pox in a child aged 3.8 years with secondary infection of the skin of the right subscapular region and subcutaneous fat (phlegmon of the trunk) of streptococcal etiology. The diagnosis of varicella was confirmed by the detection of Varicella-Zoster virus DNA by PCR from the skin. Surgical treatment was performed — opening and drainage of phlegmon, purulent-serous discharge was obtained, sowing was performed, Streptococcus pyogenes was isolated. The child received antibiotic therapy — cefepime sulbactam, amikacin, acyclovir, infusion therapy, local treatment. Conclusions. The given clinical case demonstrates the development of a severe bacterial complication of chicken pox, which required surgical treatment and substantiates the need for vaccination against chicken pox and its possible complications.
Multiscale optical imaging of rare-earth-doped nanocomposites in a small animal model (2018)

Rare-earth-doped nanocomposites have appealing optical properties for use as biomedical contrast agents, but few systems exist for imaging these materials. We describe the design and characterization of (i) a preclinical system for whole animal in vivo imaging and (ii) an integrated optical coherence tomography/confocal microscopy system for high-resolution imaging of ex vivo tissues. We demonstrate these systems by administering erbium-doped nanocomposites to a murine model of metastatic breast cancer. Short-wave infrared emissions were detected in vivo and in whole organ imaging ex vivo. Visible upconversion emissions and tissue autofluorescence were imaged in biopsy specimens, alongside optical coherence tomography imaging of tissue microstructure. We anticipate that this work will provide guidance for researchers seeking to image these nanomaterials across a wide range of biological models.
An immunoassay for the study of DNA-binding activities of herpes simplex virus protein ICP8 (1985)

An immunoassay was used to examine the interaction between a herpes simplex virus protein, ICP8, and various types of DNA. The advantage of this assay is that the protein is not subjected to harsh purification procedures. We characterized the binding of ICP8 to both single-stranded (ss) and double-stranded (ds) DNA. ICP8 bound ss DNA fivefold more efficiently than ds DNA, and both binding activities were most efficient in 150 mM NaCl. Two lines of evidence indicate that the binding activities were not identical: (i) ds DNA failed to complete with ss DNA binding even with a large excess of ds DNA; (ii) Scatchard plots of DNA binding with various amounts of DNA were fundamentally different for ss DNA and ds DNA. However, the two activities were related in that ss DNA efficiently competed with the binding of ds DNA. We conclude that the ds DNA-binding activity of ICP8 is probably distinct from the ss DNA-binding activity. No evidence for sequence-specific ds DNA binding was obtained for either the entire herpes simplex virus genome or cloned viral sequences.
Expression cloning of fungal enzyme genes; a novel approach for efficient isolation of enzyme genes of industrial relevance (1997)

Expression cloning is a relatively new method for fast and efficient cloning of enzyme genes from fungi that are known to make complex enzyme mixtures. In contrast to traditional cloning methods that are usually dependent on knowledge of at least a partial amino acid sequence in order to synthesize appropriate DNA probes or primers, the expression cloning method solely relies on access to reliable and sensitive enzyme assays. A representative expression cDNA library is made in Saccharomyces cerevisiae form the donor strain and relevant cDNA clones are detected directly based on the encoded enzyme activity. Thus, time-consuming enzyme purification and characterization steps are avoided. The method has been applied on the characterization of extracellular enzyme genes from the filamentous fungus Aspergillus aculeatus and has resulted in the isolation of 20 different enzyme genes such as endo-glucanases, xylanases, pectinases, proteases, hemicellulases and rhamnogalacturonan-degrading enzymes. All enzymes have been expressed in Aspergillus oryzae, purified and characterized. In the present review a description of the expression cloning technique will be given as well as examples of how the technique has been used in the exploration and characterization of a commercial enzyme product that is known to consist of a complex mixture of more than 25 different enzyme activities.
Effect of radon exposure on asthma morbidity in the School Inner‐City Asthma study (2023)

In asthmatic children, radon may be associated with increased asthma morbidity, suggesting radon may be a modifiable environmental risk factor for airway inflammation.