gebhart/patrepeval huggingface dataset:
TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine (2013)

Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies.
Xanthine Phosphoribosyltransferase from Leishmania donovani (1999)

Xanthine phosphoribosyltransferase (XPRT) from Leishmania donovani is a unique enzyme that lacks a mammalian counterpart and is, therefore, a potential target for antiparasitic therapy. To investigate the enzyme at the molecular and biochemical level, a cDNA encoding the L. donovani XPRT was isolated by functional complementation of a purine auxotroph of Escherichia coli that also harbors deficiencies in the prokaryotic phosphoribosyltransferase (PRT) activities. The cDNA was then used to isolate the XPRT genomic clone. XPRT encodes a 241-amino acid protein exhibiting approximately 33% amino acid identity with the L. donovani hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and significant homology with other HGPRT family members. Southern blot analysis revealed that XPRT was a single copy gene that co-localized with HGPRT within a 4.3-kilobase pair (kb) EcoRI fragment, implying that the two genes arose as a result of an ancestral duplication event. Sequencing of this EcoRI fragment confirmed that HGPRT and XPRT were organized in a head-to-tail arrangement separated by an approximately 2.2-kb intergenic region. Both the 3.2-kb XPRT mRNA and XPRT enzyme were significantly up-regulated in Deltahgprt and Deltahgprt/Deltaaprt L. donovani mutants. Genetic obliteration of the XPRT locus by targeted gene replacement indicated that XPRT was not an essential gene under most conditions and that the Deltaxprt null strain was competent of salvaging all purines except xanthine. XPRT was overexpressed in E. coli and the recombinant protein purified to homogeneity. Kinetic analysis revealed that the XPRT preferentially phosphoribosylated xanthine but could also recognize hypoxanthine and guanine. K(m) values of 7.1, 448.0, and >100 microM and k(cat) values of 3.5, 2.6, and approximately 0.003 s(-1) were calculated for xanthine, hypoxanthine, and guanine, respectively. The XPRT gene and XPRT protein provide the requisite molecular and biochemical reagents for subsequent studies to validate XPRT as a potential therapeutic target.
Challenges and advances in the assessment of the disposition of antibody‐drug conjugates (2015)

Antibody-drug conjugates (ADCs) are a rapidly growing therapeutic platform for the treatment of cancer. ADCs consist of a cytotoxic small molecule drug linked to an antibody to provide targeted delivery of the cytotoxic agent to the tumor. Understanding the pharmacokinetics (PK) and pharmacodynamics (PD) of ADCs is crucial in their design to optimize dose and regimen, to maximize efficacy and to minimize toxicity in patients. Significant progress has been made in recent years in this area, however, many fundamental questions still remain. This review discusses factors to consider while assessing the disposition of ADCs, and the unique challenges associated with these therapeutics. Current tools that are available and strategies to enable appropriate assessment are also discussed.
SHP2 inhibitor PHPS1 protects against atherosclerosis by inhibiting smooth muscle cell proliferation (2018)

The SHP2 inhibitor PHPS1 exerts a protective effect against atherosclerosis by reducing VSMC proliferation via SHP2/ERK pathway activation.
Wavelength-tunable microbolometers with metamaterial absorbers (2009)

Microbolometers are modified by metallic resonant absorber elements, leading to an enhanced responsivity at selectable wavelengths. The dissipative energy absorption of tailored metamaterials allows for engineering the response of conventional bolometer microbridges. The absorption peak position and height are determined by the geometry of the metamaterial. Square-shaped metal/dielectric/metal stacks as absorber elements show spectral resonances at wavelengths between 4.8 and 7.0 microm in accordance with numerical simulations. Total peak absorptions of 0.8 are obtained. The metamaterial modified bolometers are suitable for multispectral thermal imaging systems in the mid-IR and terahertz regime.
TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. (1995)

The t(12;21)(p13;q22) is identified by routine cytogenetics in less than 0.05% of pediatric acute lymphoblastic leukemia (ALL) patients. This translocation encodes a TEL/AML-1 chimeric product comprising the helix-loop-helix domain of TEL, a member of the ETS-like family of transcription factors, fused to AML-1, the DNA-binding subunit of the AML-1/CBF beta transcription factor complex. Both TEL and AML-1 are involved in several myeloid leukemia-associated translocations with AML-1/CBF beta being altered in 20-30% of de novo acute myeloid leukemia (AML) cases. We now demonstrate that a TEL/AML1 chimeric transcript encoded by a cryptic t(12;21) is observed in 22% of pediatric ALL, making it the most common genetic lesion in these patients. Moreover, TEL/AML1 expression defined a distinct subgroup of patients characterized by an age between 1 and 10 years, B lineage immunophenotype, non-hyperdiploid DNA content and an excellent prognosis. These data demonstrate that molecular diagnostic approaches are invaluable in identifying clinically distinct subgroups, and that the AML1/CBF beta transcription complex is the most frequent target of chromosomal rearrangements in human leukemia.
Porous Alginate Hydrogel Functionalized with Virus as Three-Dimensional Scaffolds for Bone Differentiation (2012)

In regenerative medicine, a synthetic extracellular matrix is crucial for supporting stem cells during its differentiation process to integrate into surrounding tissues. Hydrogels are used extensively in biomaterials as synthetic matrices to support the cells. However, to mimic the biological niche of a functional tissue, various chemical functionalities are necessary. We present here, a method of functionalizing a highly porous hydrogel with functional groups by mixing the hydrogel with a plant virus, tobacco mosaic virus (TMV), and its mutant. The implication of this process resides with the three important features of TMV: its well-defined genetic/chemical modularity, its multivalency (TMV capsid is composed of 2130 copies of identical subunits), and its well-defined structural features. Previous studies utilizing the native TMV on two-dimensional supports accelerated mesenchymal stem cell differentiation, and surfaces modified with genetically modified viral particles further enhanced cell attachment and differentiation. Herein we demonstrate that functionalization of a porous alginate scaffold can be achieved by the addition of viral particles with minimal processing and downstream purifications, and the cell attachment and differentiation within the macroporous scaffold can be effectively manipulated by altering the peptide or small molecule displayed on the viral particles.
Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload (2001)

Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.
COPD Unwound (2005)

In this issue of the Journal, Ito and colleagues show that the proinflammatory state in severe stages of chronic obstructive pulmonary disease (COPD) is related to chromatin unwinding.1 To review basic gene regulation quickly, the balance between histone deacetylases (HDACs) and histone acetylases determines the state of histone acetylation. Acetylated histone prompts the unwinding of chromatin, allowing transcriptional complexes to bind to DNA and generate messenger RNA. In COPD, oxidants from cigarette smoke or inflammatory cells modify and deactivate HDAC2 in lung macrophages, allowing RNA polymerase II and nuclear factor-κB (NF-κB) to bind to DNA and promote transcription of matrix . . .
A Method to Automate Cloud Application Management Patterns (2014)

\n Management patterns are a well-established concept to document\n reusable solutions for recurring application management issues in a\n certain context. Their generic nature provides a powerful means to\n describe application management knowledge in an abstract fashion\n that can be refined for individual use cases manually. However,\n manual refinement of abstract management patterns for concrete\n applications prevents applying the concept of patterns efficiently\n to the domain of Cloud Computing, which requires a fast and\n immediate execution of arising management tasks. Thus, the\n application of management patterns must be automated to fulfill\n these requirements. In this paper, we present a method that guides\n the automation of Cloud Application Management Patterns using the\n Management Planlet Framework, which enables applying them fully\n automatically to individual running applications. We explain how\n existing management patterns can be implemented as Automated\n Management Patterns and show how these implementations can be tested\n afterwards to ensure their correctness. To validate the approach, we\n conduct a detailed case study on a real migration scenario.\n
Effect of aging on susceptibility of low-density lipoproteins to oxidation (1995)

According to the Adult Treatment Panel of the National Cholesterol Education Program, age is a major risk factor for heart disease. To assess the relation between age and LDL oxidizability, we studied copper-mediated LDL oxidation in 13 healthy elderly subjects (> 59 years) and 13 sex-matched healthy young controls (< 30 years). Total and LDL-cholesterol concentrations were increased in elderly subjects. The time course of copper-mediated LDL oxidation showed no significant differences between the two groups as assessed by formation of conjugated dienes, lipid peroxides, and apolipoprotein B fluorescence. Kinetics of LDL oxidation as quantified by lag time, oxidation rate, and maximal oxidation were not significantly different between the elderly and young groups. Although the concentrations of 16:0, 18:0, 18:1, 18:3, and 20:4 and total polyunsaturated fatty acids were significantly higher in the elderly group, LDL fatty acid concentrations were similar in both groups. Lipid-standardized alpha-tocopherol, beta-carotene, and ascorbate concentrations were not significantly different between the two groups. The findings of the present study suggest that in the healthy elderly, LDL oxidation may not be a crucial mediator for atherogenesis.
PWR secondary water chemistry guidelines in Japan - Purpose and technical background (2019)

In the more than 40 years of operational history of pressurized water reactors (PWRs) in Japan, sustainable development of water chemistry technologies has resulted in the world's highest secondary system component integrity; additionally, secondary system components, especially steam generator (SG) tubing, with excellent material integrity have been developed to prevent leakage of radioactive contamination from the primary to the secondary system and to maintain the heat removal function of the secondary system. Although reasonable control and diagnostic parameters for water chemistry are utilized by each PWR owner, the specific values are not shared. To ensure reliable PWR operation and to achieve the highest safety level, relevant members of the Standards Committee and the related committee organized by the Atomic Energy Society of Japan (AESJ) decided to establish water chemistry guidelines for PWRs. The Japanese PWR secondary water chemistry guidelines provide strategies for improving material integrity and the heat removal function. The guidelines also provide reasonable "action levels" for control parameters and "control values" and "diagnostic values" for multiple parameters, and they stipulate the responses when these levels are exceeded. Specifically, "conditioning parameters" are adopted in the guidelines. Good operational practice conditions are also discussed with reference to long-term experience. This paper introduces the purpose, technical background and framework of preliminary secondary water chemistry guidelines for Japanese PWRs. Addition, the differences in bases of parameter settings between the Japanese and overseas guidelines are discussed.
Lactoferrin regulates the immune responses in post-surgical patients. (2001)

The effect of oral administration of lactoferrin (LF) was studied to determine if it could modify post-surgical immune response. The action of LF was evaluated in 18 LF-treated patients vs 28 placebo counterparts. Patients (women and men, mean age 50 years) were given daily oral doses (20 mg each) of LF for 5 consecutive days prior to thyroid surgery. The following immune response parameters were determined in blood samples taken from the patients day before, day after, and 5-7 days following surgery: cell morphology, the proliferative response of peripheral blood mononuclear cells to phytohemagglutinin, and the spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). As a consequence of the thyroid surgery, the total leukocyte count increased on the post-operative day by about 50% in all patients and the percentage of lymphocytes fell by 26 and 35% in the control vs LF-treated group. The content of neutrophils, on the other hand, elevated on day 1 post-operation by 51 and 68%, respectively. The percent of neutrophil precursors was markedly higher in LF-treated patients, particularly on the day before and the day after surgery (4.1 and 4.8 vs 2.5 and 3.7%, respectively). The post-surgical values were, however, comparable in both groups for neutrophils. The proliferative response of lymphocytes showed a slight decrease in the control group and an increase in the LF-treated patients on day 5 post-operation (20% over control group). LPS-induced TNF-alpha production was higher in LF-treated patients both one day before and one day following surgery (28 and 24%, respectively). LPS-induced IL-6 production was comparable in both placebo and LF-treated patients before surgery, however, on day 1 and 5 following surgery, the production of IL-6 was higher in LF-treated patients by 65 and 27%, respectively. Taken together, the data presented in this study revealed an increased immune responsiveness in all patients treated with LF and subjected to thyroid surgery. This suggests that treatment with LF could constitute an effective protective measure against post-surgical complications.
Accelerated iterative transmission CT reconstruction using an ordered subsets convex algorithm (1998)

Iterative maximum likelihood (ML) transmission computed tomography algorithms have distinct advantages over Fourier-based reconstruction, but unfortunately require increased computation time. The convex algorithm [1] is a relatively fast iterative ML algorithm but it is nevertheless too slow for many applications. Therefore, an acceleration of this algorithm by using ordered subsets of projections is proposed [ordered subsets convex algorithm (OSC)]. OSC applies the convex algorithm sequentially to subsets of projections. OSC was compared with the convex algorithm using simulated and physical thorax phantom data. Reconstructions were performed for OSC using eight and 16 subsets (eight and four projections/subset, respectively). Global errors, image noise, contrast recovery, and likelihood increase were calculated. Results show that OSC is faster than the convex algorithm, the amount of acceleration being approximately proportional to the number of subsets in OSC, and it causes only a slight increase of noise and global errors in the reconstructions. Images and image profiles of the reconstructions were in good agreement. In conclusion, OSC and the convex algorithm result in similar image quality but OSC is more than an order of magnitude faster.
The enzyme-like catalytic activity of cerium oxide nanoparticles and its dependency on Ce<sup>3+</sup> surface area concentration (2018)

Cerium oxide nanoparticles are known to catalyze the decomposition of reactive oxygen species such as the superoxide radical and hydrogen peroxide. Herein, we examine the superoxide dismutase (SOD) and catalase (CAT) mimetic catalytic activities of nanoceria and demonstrate the existence of generic behaviors. For particles of sizes 4.5, 7.8, 23 and 28 nm, the SOD and CAT catalytic activities exhibit the characteristic shape of a Langmuir isotherm as a function of cerium concentration. The results show that the catalytic effects are enhanced for smaller particles and for the particles with the largest Ce3+ fraction. The SOD-like activity obtained from the different samples is found to superimpose on a single master curve using the Ce3+ surface area concentration as a new variable, indicating the existence of particle independent redox mechanisms. For the CAT assays, the adsorption of H2O2 molecules at the particle surface modulates the efficacy of the decomposition process and must be taken into account. We design an amperometry-based experiment to evaluate the H2O2 adsorption at nanoceria surfaces, leading to the renormalization of the particle specific area. Depending on the particle type the amount of adsorbed H2O2 molecules varies from 2 to 20 nm-2. The proposed scalings are predictive and allow the determination of the SOD and CAT catalytic properties of cerium oxide solely from physicochemical features.
A Comparison of Methods for Filling Gaps in Hourly Near-Surface Air Temperature Data (2012)

Abstract Near-surface air temperature observations often have periods of missing data, and many applications using these datasets require filling in all missing periods. Multiple methods are available to fill missing data, but the comparative accuracy of these approaches has not been assessed. In this comparative study, five techniques were used to fill in missing temperature data: spatiotemporal correlations in the form of empirical orthogonal functions (EOFs), time series diurnal interpolation, and three variations of lapse rate–based filling. The method validation used sets of hourly surface temperature observations in complex terrain from five regions. The most accurate method for filling missing data depended on the number of available stations and the number of hours of missing data. Spatiotemporal correlations using EOF reconstruction were most accurate provided that at least 16 stations were available. Temporal interpolation was the most accurate method when only one or two stations were available or for 1-h gaps. Lapse rate–based filling was most accurate for intermediate numbers of stations. The accuracy of the lapse rate and EOF methods was found to be sensitive to the vertical separation of stations and the degree of correlation between them, which also explained some of the regional differences in performance. Horizontal distance was less significantly correlated with method performance. From these findings, guidelines are presented for choosing a filling method based on the duration of the missing data and the number of stations.
Oligodendrocyte development and the onset of myelination in the human fetal brain (2009)

Oligodendrocytes are cells that myelinate axons, providing saltatory conduction of action potentials and proper function of the central nervous system. Myelination begins prenatally in the human, and the sequence of oligodendrocyte development and the onset of myelination are not thoroughly investigated. This knowledge is important to better understand human diseases, such as periventricular leukomalacia, one of the leading causes of motor deficit in premature babies, and demyelinating disorders such as multiple sclerosis (MS). In this review we discuss the spatial and temporal progression of oligodendrocyte lineage characterized by the expression of specific markers and transcription factors in the human fetal brain from the early embryonic period (5 gestational weeks, gw) until midgestation (24 gw). Our in vitro evidence indicated that a subpopulation of human oligodendrocytes may have dorsal origin, from cortical radial glia cells, in addition to their ventral telencephalic origin. Furthermore, we demonstrated that the regulation of myelination in the human fetal brain includes positive and negative regulators. Chemokines, such as CXCL1, abundant in proliferative zones during brain development and in regions of remyelination in adult, are discussed in the view of their potential roles in stimulating oligodendrocyte development. Other signals are inhibitory and may include, but are not limited to, polysialic acid modification of the neural cell adhesion molecule on axons. Overall, important differences in temporal and spatial distribution and regulatory signals for oligodendrocyte differentiation exist between human and rodent brains. Those differences may underlie the unique susceptibility of humans to demyelinating diseases, such as MS.
Immersive haptic interaction with media (2010)

New 3D video representations enable new modalities of interaction, such as haptic interaction, with 2D and 3D video for truly immersive media applications. Haptic interaction with video includes haptic structure and haptic motion for new immersive experiences. It is possible to compute haptic structure signals from 3D scene geometry or depth information. This paper introduces the concept of haptic motion, as well as new methods to compute haptic structure and motion signals for 2D video-plus-depth representation. The resulting haptic signals can be rendered using a haptic cursor attached to a 2D or 3D video display.