gebhart/patrepeval huggingface dataset:
Tent-induced perturbations on areal density of implosions at the National Ignition Facilitya) (2015)

Areal density non-uniformities seeded by time-dependent drive variations and target imperfections in Inertial Confinement Fusion (ICF) targets can grow in time as the capsule implodes, with growth rates that are amplified by instabilities. Here, we report on the first measurements of the perturbations on the density and areal density profiles induced by the membranes used to hold the capsule within the hohlraum in indirect drive ICF targets. The measurements are based on the reconstruction of the ablator density profiles from 2D radiographs obtained using pinhole imaging coupled to area backlighting, as close as 150 ps to peak compression. Our study shows a clear correlation between the modulations imposed on the areal density and measured neutron yield, and a 3× reduction in the areal density perturbations comparing a high-adiabat vs. low-adiabat pulse shape.
Chemokines in disease : biology and clinical research (1999)

Caroline Hébert and a panel of key experimentalists and clinical investigators comprehensively review the state-of-the-art in the chemokine field, ranging from the effects of chemokines and their receptors in retroviral infections, to their role in inflammation, angiogenesis/angiostasis, and tumor cell biology. The book examines in detail fifteen recently identified chemokines and elucidates the role of chemokine function in vivo from animal experiments. Animal models are also used to explore how chemokines operate in a variety of chronic and acute inflammatory diseases and in noninflammatory processes. A detailed review of the emerging role of chemokines in viral biology is also presented, with emphasis on HIV biology and novel therapeutic possibilities. Chemokines in Disease: Biology and Clinical Research summarizes the rapidly expanding knowledge of a dazzling array of chemokines and provides fresh insights into the development of powerful new drugs for treating a wide spectrum of diseases
State of the art and challenges in sequence based T-cell epitope prediction (2010)

Sequence based T-cell epitope predictions have improved immensely in the last decade. From predictions of peptide binding to major histocompatibility complex molecules with moderate accuracy, limited allele coverage, and no good estimates of the other events in the antigen-processing pathway, the field has evolved significantly. Methods have now been developed that produce highly accurate binding predictions for many alleles and integrate both proteasomal cleavage and transport events. Moreover have so-called pan-specific methods been developed, which allow for prediction of peptide binding to MHC alleles characterized by limited or no peptide binding data. Most of the developed methods are publicly available, and have proven to be very useful as a shortcut in epitope discovery. Here, we will go through some of the history of sequence-based predictions of helper as well as cytotoxic T cell epitopes. We will focus on some of the most accurate methods and their basic background.
GPR55 ligands promote receptor coupling to multiple signalling pathways (2010)

Our data help to resolve some of the issues surrounding the pharmacology of cannabinoid ligands at GPR55 and highlight some differences in effector coupling associated with distinct GPR55 ligands.
Optimal material control in an assembly system with component commonality (2001)

Abstract Allocation of scarce common components to finished product orders is central to the performance of assembly systems. Analysis of these systems is complex, however, when the product master schedule is subject to uncertainty. In this paper, we analyze the cost—service performance of a component inventory system with correlated finished product demands, where component allocation is based on a fair shares method. Such issuing policies are used commonly in practice. We quantify the impact of component stocking policies on finished product delays due to component shortages and on product order completion rates. These results are used to determine optimal base stock levels for components, subject to constraints on finished product service (order completion rates). Our methodology can help managers of assembly systems to (1) understand the impact of their inventory management decisions on customer service, (2) achieve cost reductions by optimizing their inventory investments, and (3) evaluate supplier performance and negotiate contracts by quantifying the effect of delivery lead times on costs and customer service. © 2001 John Wiley &amp; Sons, Inc. Naval Research Logistics 48:409–429, 2001
Synergistic effect of 4-hydroperoxycyclophosphamide and etoposide on a human promyelocytic leukemia cell line (HL-60) demonstrated by computer analysis. (1985)

Autologous stem cell transplantation using cryopreserved bone marrow offers the opportunity to rescue patients from hematopoietic toxicity caused by intensive chemotherapy. This approach is potentially useful for high-risk leukemias as well as for other cancers. The development of suitable methods for purging malignant cells from the bone marrow will offer a better chance of success for autologous stem cell transplantation. In this paper, we describe our efforts at purging myeloid cells. HL-60, a promyelocytic leukemia cell line, was used as a model. 4-Hydroperoxycyclophosphamide (4-HC) and VP-16-213 (VP-16) (either alone or in combination) were used to treat HL-60 cells and normal bone marrow. The cytotoxic effect of 4-HC (29.2 micrograms/ml; 100 microM) upon the HL-60 cell line was 99.8 +/- 0.12% (SE), and the colony-forming units-granulocyte, macrophage (CFU-cs) of normal bone marrow was inhibited by 82.5%. VP-16, at a concentration of 25 micrograms/ml (42.5 microM), can kill 99% of HL-60 cells and inhibit 72.7% of the CFU-cs. A drug mixture containing 4-HC (29.2 micrograms/ml) and VP-16 (10 micrograms/ml) (combination ratio, 1:0.342) reduces HL-60 cells to an undetectable number, and the CFU-cs were inhibited by 87.2%. The laboratory data were further analyzed for the synergistic effect of these two drugs by quantitative determination of the median effect plot and the multiple drug equation recently described by Chou and Talalay (Adv. Enz. Regul., 22: 27-55, 1984). Interactions of two drugs at different effect levels and at different combination ratios were then determined by computer simulation. At high effect levels, 4-HC and VP-16 in combination gave a synergistic cytocidal effect on HL-60 leukemic cells and gave an antagonistic inhibitory effect on normal bone marrow CFU-cs. This combination greatly increases the safety margin. Computer simulation of a dose effect relationship has also shown that the 4-HC:VP-16 combination ratio of 1:0.342 yields a better selective effect than a ratio of 1:0.856. This quantitative analysis suggests that the combination of these two drugs at the selected dose level offers a good method for purging nonlymphoblastic leukemia cells.
IR Supercontinuum Generation in As-Se Photonic Crystal Fiber (2005)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text L. B. Shaw, V. Q. Nguyen, J. S. Sanghera, I. D. Aggarwal, P. A. Thielen, and F. H. Kung, "IR Supercontinuum Generation in As-Se Photonic Crystal Fiber," in Advanced Solid-State Photonics (TOPS), C. Denman and I. Sorokina, eds., Vol. 98 of OSA Trends in Optics and Photonics (Optica Publishing Group, 2005), paper 864. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Safety of Statins (2004)

Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, however, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions.
Survival of Plant Seeds, Their UV Screens, and nptII DNA for 18 Months Outside the International Space Station (2012)

The plausibility that life was imported to Earth from elsewhere can be tested by subjecting life-forms to space travel. Ultraviolet light is the major liability in short-term exposures (Horneck et al., 2001 ), and plant seeds, tardigrades, and lichens-but not microorganisms and their spores-are candidates for long-term survival (Anikeeva et al., 1990 ; Sancho et al., 2007 ; Jönsson et al., 2008 ; de la Torre et al., 2010 ). In the present study, plant seeds germinated after 1.5 years of exposure to solar UV, solar and galactic cosmic radiation, temperature fluctuations, and space vacuum outside the International Space Station. Of the 2100 exposed wild-type Arabidopsis thaliana and Nicotiana tabacum (tobacco) seeds, 23% produced viable plants after return to Earth. Survival was lower in the Arabidopsis Wassilewskija ecotype and in mutants (tt4-8 and fah1-2) lacking UV screens. The highest survival occurred in tobacco (44%). Germination was delayed in seeds shielded from solar light, yet full survival was attained, which indicates that longer space travel would be possible for seeds embedded in an opaque matrix. We conclude that a naked, seed-like entity could have survived exposure to solar UV radiation during a hypothetical transfer from Mars to Earth. Chemical samples of seed flavonoid UV screens were degraded by UV, but their overall capacity to absorb UV was retained. Naked DNA encoding the nptII gene (kanamycin resistance) was also degraded by UV. A fragment, however, was detected by the polymerase chain reaction, and the gene survived in space when protected from UV. Even if seeds do not survive, components (e.g., their DNA) might survive transfer over cosmic distances.
Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment. (1995)

To determine events that transpire during the earliest stages of human T cell development, we have studied fetal tissues before (7 wk), during (8.2 wk), and after (9.5 wk to birth) colonization of the fetal thymic rudiment with hematopoietic stem cells. Calculation of the approximate volumes of the 7- and 8.2-wk thymuses revealed a 35-fold increase in thymic volumes during this time, with 7-wk thymus height of 160 microM and volume of 0.008 mm3, and 8.2-wk thymus height of 1044 microM and volume of 0.296 mm3. Human thymocytes in the 8.2-wk thymus were CD4+ CD8 alpha+ and cytoplasmic CD3 epsilon+ cCD3 delta+ CD8 beta- and CD3 zetta-. Only 5% of 8-wk thymocytes were T cell receptor (TCR)-beta+, < 0.1% were TCR-gamma+, and none reacted with monoclonal antibodies against TCR-delta. During the first 16 wk of gestation, we observed developmentally regulated expression of CD2 and CD8 beta (appearing at 9.5 wk), CD1a,b, and c molecules (CD1b, then CD1c, then CD1a), TCR molecules (TCR-beta, then TCR-delta), CD45RA and CD45RO isoforms, CD28 (10 wk), CD3 zeta (12-13 wk), and CD6 (12,75 wk). Whereas CD2 was not expressed at the time of initiation of thymic lymphopoiesis, a second CD58 ligand, CD48, was expressed at 8.2 wk, suggesting a role for CD48 early in thymic development. Taken together, these data define sequential phenotypic and morphologic changes that occur in human thymus coincident with thymus colonization by hematopoietic stem cells and provide insight into the molecules that are involved in the earliest stages of human T cell development.
Uptake of Adenoviral Vectors via Fibroblast Growth Factor Receptors Involves Intracellular Pathways That Differ from the Targeting Ligand (2001)

Target-specific delivery of adenoviral gene therapy vectors has been achieved by introducing basic fibroblast growth factor (FGF2) onto viral capsids. FGF2-retargeted vectors enter the cell through high-affinity FGF receptors while normal adenoviral receptor interactions are ablated. In addition, FGF2-mediated targeting permits a higher level of transgene expression and in vivo efficacy. We now present studies on the intracellular pathways and mechanisms of transduction by FGF2-retargeted adenovirus. FGF2 retargeting results in increased virion entry. Nuclear delivery is also increased, but to a level that is directly proportional to virion entry. In addition, after entry, the retargeted particle rapidly localizes to the nucleus in a time frame similar to that of adenovirus alone. Transgene expression is always enhanced with FGF2-mediated delivery, whether overall transduction of the population is increased, equivalent, or decreased relative to nontargeted adenoviral vectors. However, the increase in transgene expression does not correlate quantitatively with enhanced cellular entry, indicating that other factors may influence transgene expression levels. The increase in transgene expression occurs only when the FGF2-retargeting moiety is physically complexed with the adenoviral vector, indicating a requirement for a spatial link between the ligand and the virus particle. The FGF2-adenoviral complex activates the FGF receptor-mediated proliferative signaling cascade, but this signal transduction is not required for the enhanced level of gene expression observed after FGF2-mediated delivery. These findings emphasize that, in addition to altering receptor tropism, the influence of FGF2 retargeting extends to intracellular adenoviral trafficking pathways. Although the increased delivery of virions into the cell and nucleus contributes to the enhanced transgene expression observed with FGF2 retargeting, other as yet undefined cellular mechanisms also contribute to this process.
Thrombospondin-4 and Its Variants (2003)

TSP-4 is expressed by vascular cells and influences the vessel wall by modulating the proliferation of ECs and smooth muscle cells. The A387P substitution is a "gain-of-function" mutation, favoring a form of TSP-4 that interferes with EC adhesion and proliferation and may thereby be proatherogenic.
Activation of factor IX bound to cultured bovine aortic endothelial cells. (1984)

Previous studies have shown that factor IX and its activated form, factor IXa, bind to cultured vascular endothelial cells and that cell-bound factor IXa retains its procoagulant activity. The present studies provide evidence that factor IX bound to cultured bovine aortic endothelial cells can be activated. Factor IX activation was assessed by finding cleavage of the factor IX molecule on NaDodSO4/polyacrylamide gel electrophoresis and by the generation of procoagulant activity as assessed by thrombin-treated factor VIII-dependent generation of factor Xa activity. Cell-bound factor IX (0.8 micrograms per 4 X 10(8) cells per ml) could be activated by factor XIa (5 micrograms/ml) or by factor VIIa (0.1 micrograms/ml) without exogenous tissue factor when endothelial cells were treated with phorbol ester and acquired tissue factor-like procoagulant activity. Regardless of how factor IX was activated, the cell-bound factor IXa required thrombin-treated factor VIII and calcium, but not exogenous phospholipid, to activate factor X. In further experiments, factor X bound to endothelial cells specifically and reversibly with a dependence on calcium and with a lower affinity (half-maximal at 480 nM) than factor IX. At saturation, 9.1 X 10(6) factor X molecules were bound per cell. After activation of factor X by factor IXa, approximately 50% of the factor Xa formed could be eluted from the cells by 10 mM EDTA, suggesting that the factor Xa was cell associated. These observations indicate that endothelial cells can bind and promote the activation of factors IX and X in the absence of platelets or exogenous phospholipid.
Prolactin antagonist-endostatin fusion protein as a targeted dual-functional therapeutic agent for breast cancer. (2003)

In previous studies (Chen, W. Y. et al., Clin. Cancer Res., 5:3583-3593, 1999; Chen, N Y. et al., Int. J. Oncol., 20:813-818, 2002), we have demonstrated the ability of the human prolactin (hPRL) antagonist, G129R, to inhibit human breast cancer cell proliferation in vitro and to slow the growth rate of tumors in mice. We further revealed that the possible mechanisms of G129R antitumor effects act through the induction of apoptosis via the regulation of bcl-2 gene expression. It has been established that to sustain tumor growth, it is necessary for the development of a network of blood vessels to bring in nutrients, a process called angiogenesis. The disruption of angiogenesis has been proven to be an effective strategy to cause regression of certain tumors. One of the best-studied angiogenesis inhibitors is endostatin, which acts through the inhibition of endothelial cells. In this study, we combine the anti-breast tumor effects of G129R and the antiangiogenic effects of endostatin by creating a novel fusion protein (G129R-endostatin) specifically for breast cancer therapy. The data presented here demonstrated that this novel fusion protein was able to bind to the PRL receptor (PRLR) on T-47D human breast cancer cells and inhibit the signal transduction induced by PRL. At the same time, G129R-endostatin inhibited human umbilical vein endothelial cell (HUVEC) proliferation and disrupted the formation of endothelial tube structures with potency similar to that of endostatin. More importantly, the therapeutic efficacy of G129R-endostatin was confirmed using a mouse breast cancer cell line 4T1 in vivo. G129R-endostatin has a significantly prolonged serum half-life as compared with that of G129R or endostatin alone, and exhibited greater tumor inhibitory effects than G129R and endostatin individually or in combination. Taken together, these data demonstrate the dual therapeutic effects of G129R-endostatin, and suggests that this fusion protein has great promise as a novel anti-breast cancer agent.
Expression of p21 ras oncoproteins in human cancers. (1986)

The expression of proteins encoded by ras oncogenes was examined in 52 fresh human tumors of 19 different types using antibodies generated to different peptide domains of ras proteins of molecular weight 21,000 (p21). Proteins related to ras genes were detected in 90% of tested tumors. In 21% of tumors there were high levels of ras p21 of greater than 40% of the level in a Harvey murine sarcoma virus transformed cell line. Predominance of either cellular Ha-ras or other ras p21s was found in 20 and 14% of tumors, respectively, and predominance of p21 other than Ha-ras was frequent in breast cancers. Abnormal electrophoretic mobility of p21 was observed in two cancers, and a novel rapidly migrating ras p21 was found in a rare malignant fibrohistiocytoma.
“Upper Limits of Normal” Antistreptolysin O and Antideoxyribonuclease B Titers (1971)

"Upper limits of normal" antistreptolysin O (ASO) and antideoxyribonuclease (ADN) B titers were determined on serum specimens from various age groups of pediatric patients with no history of a recent streptococcal infection and on healthy adult hospital employees. The upper limit of normal value is that level of antibody titer exceeded by no more than 15% of the total subjects in each age group. This value varies with the age of the subject, and the most pronounced differences are between the values of preschool age children, school age children, and adults. The upper limit of normal values for these groups were as follows: preschool age, ASO = 85(100); ADN B = 60(50); school age, ASO = 170(166); ADN B=1 70(166); and adult, ASO = 85(100); ADN B = 85(100).
[Diagnosis and arthroscopic treatment of osteochondral lesions of the talus]. (2008)

MRI could improve the accuracy of diagnosis. The results of arthroscopic treatment for OLT are satisfactory.
Expression and Regulation of Small Proline-Rich Protein 2 in Allergic Inflammation (2005)

Asthma is a complex inflammatory pulmonary disorder that is on the rise despite intense ongoing research. We aimed to elucidate novel pathways involved in the pathogenesis of asthma. Employing asthma models induced by different allergens (ovalbumin and Aspergillus fumigatus), we uncovered the involvement of two members of the small proline-rich protein (SPRR) family, SPRR2a and SPRR2b, known to be involved in epithelial differentiation but not allergic disease. In situ hybridization revealed induction of SPRR2 signal in a subset of bronchial epithelial cells and mononuclear cells associated with inflammation after allergen challenge. Allergen-induced SPRR2 mRNA accumulation in the lung occurred in a time-dependent manner, with peak expression 10-96 h after a second ovalbumin challenge. Transgenic overexpression of interleukin (IL)-13 in the lungs resulted in a marked increase of SPRR2 expression, and allergen-induced SPRR2 expression was significantly decreased in IL-13-deficient mice. Studies in gene-targeted mice revealed that allergen-induced SPRR2 was dependent upon STAT6. Finally, we aimed to determine if the induction of SPRR2 by allergen was tissue specific. Notably, SPRR2 was markedly increased in the small intestine after induction of allergic gastrointestinal inflammation. Thus, SPRR2 is an allergen- and IL-13-induced gene in experimental allergic responses that may be involved in disease pathophysiology.
Synthesis and evaluation of conformationally restricted N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamines at .sigma. receptors. 2. Piperazines, bicyclic amines, bridged bicyclic amines, and miscellaneous compounds (1993)

As a continuation of our earlier study (J. Med. Chem. 1992, 35, 4334-4343) we conformationally restricted the sigma-receptor ligand 2-(1-pyrrolidinyl)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methylethylamine (1) by incorporating it into a series of homologous piperazines 3-9 and homopiperazines 10 and 11, diazabicyclononanes and decanes, bridgehead bicyclooctanes and nonanes as well as other miscellaneous compounds. sigma-Receptor binding affinities were obtained using [3H](+)-pentazocine in guinea pig brain membrane sigma 1 sites. The studies suggest that the nitrogen lone pair orientation found in the piperazines affords the strongest binding interaction. Other nitrogen lone pair orientations or compounds representing unlikely staggered conformations of 1 [ as in 4-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[3.2.2]nonane (16)] show very weak sigma interaction. Comparison of the binding data of different N-substituted homologues of 1 with those of the 1-[2-(3,4-dichlorophenyl)ethyl]-4-alkylpiperazines suggests that the two nitrogen atoms of 1 are working in opposition to one another in terms of their sensitivity to steric bulk. The high binding affinity of the 1,4-diazabicyclo[4.3.0]nonanes 12 suggests that these may approximate the methyl and pyrrolidine ring conformations found in 1 when it is bound to the sigma receptor. Compound 12 exhibited a 4-fold enantioselectivity favoring (+)-12. The synthesis of 6,7-dichloro-2-[[2-(1-pyrrolidinyl)ethyl]amino]tetralin (19) and its desmethyl derivative 20 permitted constraint of the 3,4-dichlorophenyl and N-methyl moieties of 1 into a gauche orientation. The binding data suggests that this conformation in 1 favors strong binding interaction at sigma-receptors. sigma-Receptor Ki's ranged from 0.55 nM for 1-[2-(3,4-dichlorophenyl)ethyl]-4-n-butylpiperazine (7) to 654 nM for 16. Overall comparison of the results indicate that 1 is subject to considerable conformational freedom and suggests that the sigma receptor is not subject to rigid stereochemical restraints with 1. These results add to our earlier study where we restrained 1 using simple monocyclic heterocycles.