gebhart/patrepeval huggingface dataset:
Chronic lymphocytic leukemia cells induce defective LFA-1–directed T-cell motility by altering Rho GTPase signaling that is reversible with lenalidomide (2013)

T lymphocytes have an essential role in adaptive immunity and rely on the activation of integrin lymphocyte function-associated antigen-1 (LFA-1) to mediate cell arrest and migration. In cancer, malignant cells modify the immune microenvironment to block effective host antitumor responses. We show for the first time that CD4 and CD8 T cells from patients with chronic lymphocytic leukemia (CLL) exhibit globally impaired LFA-1-mediated migration and that this defect is mediated by direct tumor cell contact. We show that following the coculture of previously healthy T cells with CLL cells, subsequent LFA-1 engagement leads to altered Rho GTPase activation signaling by downregulating RhoA and Rac1, while upregulating Cdc42. Of clinical relevance, repair of this T-cell defect was demonstrated using the immunomodulatory drug lenalidomide, which completely rescued adhesion and motility function by restoring normal Rho GTPase activation signaling. Our report identifies a novel cancer immune evasion mechanism whereby tumor cells induce Rho GTPase signaling defects in T cells that prevent appropriate LFA-1 activation and motility. We believe these findings identify important biomarkers and highlight the clinical utility of immunotherapy to rescue normal T-cell function in CLLs that are likely to have relevance in other cancers.
Chronic blockade of endothelin A and B receptors using macitentan in experimental renovascular disease (2014)

Possibly by inducing a pro-survival renal microenvironment, macitentan increased renal microvascular density, promoted cell survival and decreased injury, which in turn improved stenotic kidney hemodynamics in our model. Our results further support the safety of using macitentan in patients with concomitant chronic renal disease and supported the feasibility of a new strategy that may preserve the stenotic kidney in RVD.
Anxiolytic and Anti-Stress Effects of Brain Prolactin: Improved Efficacy of Antisense Targeting of the Prolactin Receptor by Molecular Modeling (2001)

We provide the first evidence that prolactin is a neuromodulator of behavioral and neuroendocrine stress coping in the rat. In virgin female and male rats, intracerebral infusion of ovine prolactin (oPRL) into the lateral cerebral ventricle (intracerebroventricular) exerted an anxiolytic effect on the elevated plus-maze in a dose-dependent manner (0.1 and 1.0 microg/5 microl; p < 0.01). In contrast, downregulation of the expression of the long form of brain prolactin receptors by chronic intracerebroventricular infusion of an antisense oligodeoxynucleotide (ODN) (osmotic minipump, 0.5 microg. 0.5 microl(-1). hr(-1); 5 d) increased anxiety-related behavior on the plus-maze compared with mixed bases-treated and vehicle-treated rats (p < 0.01), again demonstrating an anxiolytic effect of PRL acting at brain level. Furthermore, in jugular vein-catheterized female rats, the stress-induced increase of corticotropin secretion was decreased after chronic intracerebroventricular infusion of oPRL (osmotic minipump, 1.0 microg. 0.5 microl(-1). hr(-1); p < 0.05) and, in contrast, was further elevated by antisense targeting of the brain prolactin receptors (p < 0.01). This provides evidence for a receptor-mediated attenuation of the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis by prolactin. The antisense ODN sequence was selected on the basis of secondary structure molecular modeling of the target mRNA to improve antisense ODN-mRNA hybridization. Receptor autoradiography confirmed the expected improvement in the efficacy of downregulation of prolactin receptor expression [empirically designed antisense, 30%; p > 0.05, not significant; adjustment of target position after mRNA modeling, 72%; p < 0.05). Taken together, prolactin acting at brain level has to be considered as a novel regulator of both emotionality and HPA axis reactivity.
PROTECTION AGAINST AN ESCHERICHIA COLI-INDUCED SEPSIS BY ALKALINE PHOSPHATASE IN MICE (2004)

Alkaline phosphatase (AP) is a phosphate transferase present in bacteria and eukaryotes. In previous studies, we have shown that AP is able to dephosphorylate lipopolysaccharide (LPS) at physiological pH levels. Because LPS is the causative agent of gram-negative sepsis, we hypothesize that AP might be used as a medication during early stages of LPS-induced septic shock. We have demonstrated protective effects of AP when this enzyme was administered simultaneously with LPS. However, a major question of anti-LPS therapies is whether they are also effective after systemic infiltration of whole bacteria and if they also act in later stages of the disease. To test this, we explored the protective effects of AP from human placenta (plAP) in a bacterial challenge model in Balb/c mice. AP was intravenously administered 20 min after a bacterial intraperitoneal inoculation of 2 to 5 x 10 CFU of Escherichia coli suspended in a 100-microL volume of saline. It was shown that AP attenuated the systemic host response upon E. coli. Body temperature was normalized as compared with untreated septic mice. Also, serum nitric oxide levels 24 h after the injection of bacteria were reduced almost to control levels in mice that received AP. Moreover, survival after 24 h was significantly higher in the AP-treated group compared with the nontreated control group.
Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus (2012)

These results demonstrate that hyperglycemic conditions inhibit C3-mediated complement effectors important in the immunological control of S. aureus. Mass spectrometric analysis reveals that the glycation state of C3 is the same regardless of glucose concentration over a one-hour time period. However, in conditions of elevated glucose C3 appears to undergo structural changes.
Synchrotron Computed Microtomography of Porous Media: Topology and Transports (1994)

Computed microtomography is applied to a piece of Fontainebleau sandstone in order to determine the geometrical structure of the pores. The topology of the void space is then derived from the tomographic image of the volume. Permeability and conductivity are computed and found in good agreement with experimental data. Perspectives offered by this new nondestructive method with a potential resolution of the order of one micrometer or less are analyzed.
Demand driven simulation: BACKSIM (1987)

A new digital simulation algorithm is presented based on the concept of demand driven simulation. Where traditional event driven simulation propagates signal values forward through a circuit in response to input pin events, demand driven simulation propagates requests for simulation values backwards both through the circuit and through time. In this manner, only those evaluations required to obtain “watched” signal values are performed. BACKSIM, the simulator based on this algorithm, has proven to be faster and more efficient than event driven simulation for every test case tried to date.
In vitro evolution of horse heart myoglobin to increase peroxidase activity (1998)

Random mutagenesis and screening for enzymatic activity has been used to engineer horse heart myoglobin to enhance its intrinsic peroxidase activity. A chemically synthesized gene encoding horse heart myoglobin was subjected to successive cycles of PCR random mutagenesis. The mutated myoglobin gene was expressed in Escherichia coli LE392, and the variants were screened for peroxidase activity with a plate assay. Four cycles of mutagenesis and screening produced a series of single, double, triple, and quadruple variants with enhanced peroxidase activity. Steady-state kinetics analysis demonstrated that the quadruple variant T39I/K45D/F46L/I107F exhibits peroxidase activity significantly greater than that of the wild-type protein with k1 (for H2O2 oxidation of metmyoglobin) of 1. 34 x 10(4) M-1 s-1 ( approximately 25-fold that of wild-type myoglobin) and k3 [for reducing the substrate (2, 2'-azino-di-(3-ethyl)benzthiazoline-6-sulfonic acid] of 1.4 x 10(6) M-1 s-1 (1.6-fold that of wild-type myoglobin). Thermal stability of these variants as measured with circular dichroism spectroscopy demonstrated that the Tm of the quadruple variant is decreased only slightly compared with wild-type (74.1 degreesC vs. 76.5 degreesC). The rate constants for binding of dioxygen exhibited by the quadruple variant are identical to the those observed for wild-type myoglobin (kon, 22.2 x 10(-6) M-1 s-1 vs. 22.3 x 10(-6) M-1 s-1; koff, 24.3 s-1 vs. 24.2 s-1; KO2, 0.91 x 10(-6) M-1 vs. 0.92 x 10(-6) M-1). The affinity of the quadruple variant for CO is increased slightly (kon, 0.90 x 10(-6) M-1s-1 vs. 0.51 x 10(-6) M-1s-1; koff, 5.08 s-1 vs. 3.51 s-1; KCO, 1.77 x 10(-7) M-1 vs. 1.45 x 10(-7) M-1). All four substitutions are in the heme pocket and within 5 A of the heme group.
Role of Intrachain Rigidity in the Plasticization of Intrinsically Microporous Triptycene-Based Polyimide Membranes in Mixed-Gas CO2/CH4 Separations (2014)

Based on high-pressure pure- and mixed-gas (50:50) CO2/CH4 separation properties of two intrinsically microporous triptycene-based polyimides (TPDA–TMPD and TPDA–6FpDA), the intrachain rigidity central to “conventional PIM” design principles is not a singular solution to intrinsic plasticization resistance. Despite the significant intrachain rigidity in TPDA–TMPD, a 300% increase in PMIX(CH4), 50% decrease in α(CO2/CH4) from 24 to 12, and continuous increase in PMIX(CO2) occurred from 4 to 30 bar. On the other hand, the more flexible and densely packed TPDA–6FpDA exhibited a slight upturn in PMIX(CO2) at 20 bar similar to a dense cellulose acetate (CA) film, also reported here, despite a 4-fold higher CO2 sorption capacity. Microstructural investigations suggest that the interconnected O2- and H2-sieving ultramicroporosity of TPDA–TMPD is more sensitive to slight CO2-induced dilations and is the physical basis for a more extensive and accelerated plasticization. Interchain rigidity, potentially by interchain interactions, is emphasized and may be facilitated by intrachain mobility.
Tidal volume effects on surfactant treatment responses with the initiation of ventilation in preterm lambs (1997)

We hypothesized that initiation of ventilation in preterm lambs with high volumes would cause lung injury and decrease the subsequent response to surfactant treatment. Preterm lambs were randomized to ventilation for 30 min after birth with 5 ml/kg (VT5), 10 ml/kg (VT10), or 20 ml/kg (VT20) tidal volumes and then ventilated with approximately 10 ml/kg tidal volumes to achieve arterial PCO2 values of approximately 50 Torr to 6 h of age. VT20 lambs had lower compliances, lower ventilatory efficiencies, higher recoveries of protein, and lower recoveries of surfactant in alveolar lavages and in surfactant that had decreased compliances when tested in preterm rabbits than VT5 or VT10 lambs. Other lambs randomized to treatment with surfactant at birth and ventilation with 6, 12, or 20 ml/kg tidal volumes for 30 min had no indicators of lung injury. An initial tidal volume of 20 ml/kg decreased the subsequent response to surfactant treatment, an effect that was prevented with surfactant treatment at birth.
Gaze-directed adaptive rendering for interacting with virtual space (1996)

This paper presents a new method of rendering for interaction with 3D virtual space with the use of gaze detection devices. In this method, hierarchical geometric models of graphic objects are constructed prior to the rendering process. The rendering process first calculates the visual acuity, which represents the importance of a graphic object for a human operator, from the gaze position of the operator. Second, the process selects a level from the set of hierachical geometric models depending on the value of visual acuity. That is, a simpler level of detail is selected where the visual acuity is lower, and a more complicated level is used where it is higher. Then, the selected graphic models are rendered on the display. This paper examines three visual characteristics to calculate the visual acuity: the central/peripheral vision, the kinetic vision, and the fusional vision. The actual implementation and our testbed system are described, as well as the details of the visual acuity model.
Navigation and Manipulation Planning Using a Visuo-Haptic Sensor on a Mobile Platform (2014)

Mobile systems interacting with objects in unstructured environments require both haptic and visual sensors to acquire sufficient scene knowledge for tasks such as navigation and manipulation. Typically, separate sensors and processing systems are used for the two modalities. We propose to acquire haptic and visual measurements simultaneously, providing naturally coherent data. For this, compression of a passive, deformable foam rod mounted on the actuator is measured visually by a low-cost camera, yielding a 1-D stress function sampled along the contour of the rod. The same camera observes the nearby scene to detect objects and their reactions to manipulation. The system is passively compliant and the complexity of the sensor subsystems is reduced. Furthermore, we present an integrated approach for navigation and manipulation on mobile platforms, which integrates haptic data from the sensor. A high-level planning graph represents both the structure of a visually acquired map, as well as manipulable obstacles. Paths within this graph represent high-level navigation and manipulation tasks, e.g., pushing of obstacles. A cost-optimal task plan is generated using standard pathfinding techniques. The approach is implemented and validated on a mobile robotic platform. Obtained forces are compared with a reference, showing high accuracy within the medium sensor range. A real-world experiment is presented, which uses the sensor for haptic exploration of obstacles in an office environment. Substantially faster task plans can be found in cluttered scenes compared with purely visual navigation.
RNAlater and flash freezing storage methods nonrandomly influence observed gene expression in RNAseq experiments (2018)

Abstract RNA-sequencing is a popular next-generation sequencing technique for assaying genome-wide gene expression profiles. Nonetheless, it is susceptible to biases that are introduced by sample handling prior gene expression measurements. Two of the most common methods for preserving samples in both field-based and laboratory conditions are submersion in RNAlater and flash freezing in liquid nitrogen. Flash freezing in liquid nitrogen can be impractical, particularly for field collections. RNAlater is a solution for stabilizing tissue for longer-term storage as it rapidly permeates tissue to protect cellular RNA. In this study, we assessed genome-wide expression patterns in 30 day old fry collected from the same brood at the same time point that were flash-frozen in liquid nitrogen and stored at −80°C or submerged and stored in RNAlater at room temperature, simulating conditions of fieldwork. We show that sample storage is a significant factor influencing observed differential gene expression. In particular, genes with elevated GC content exhibit higher observed expression levels in liquid nitrogen flash-freezing relative to RNAlater-storage. Further, genes with higher expression in RNAlater relative to liquid nitrogen experience disproportionate enrichment for functional categories, many of which are involved in RNA processing. This suggests that RNAlater may elicit a physiological response that has the potential to bias biological interpretations of expression studies. The biases introduced to observed gene expression arising from mimicking many field-based studies are substantial and should not be ignored.
CD19 Function in Early and Late B Cell Development: I. Maintenance of Follicular and Marginal Zone B Cells Requires CD19-Dependent Survival Signals (2003)

Loss of membrane-bound Ig results in the rapid onset of apoptosis in recirculating B cells. This observation implies that a competent B cell receptor (BCR) is not only required for Ag-dependent differentiation, but also for continued survival in the peripheral immune system. Expression of the B cell coreceptor, CD19, is likewise essential for key B cell differentiative events including the formation of B-1, germinal center, and marginal zone (MZ) B cells. In this study, we report that CD19 also exerts a role before Ag encounter by promoting the survival of naive recirculating B cells. This aspect of CD19 signaling was first suggested by the analysis of mixed bone marrow chimeras, wherein CD19-/- B cells fail to effectively compete with wild-type B cells to reconstitute the peripheral B cell compartment. Consistent with this observation, Bromodeoxyuridine- and CFSE-labeling studies reveal a shorter in vivo life span for CD19-/- B cells vs their wild-type counterparts. Moreover, we find that CD19 is necessary for propagation of BCR-induced survival signals and thus may contribute to homeostatic mechanisms of tonic signaling. To determine whether provision of a constitutive survival signal could compensate for the loss of CD19 in vivo, Bcl-2-transgenic mice were bred onto the CD19-/- background. Here, we observe an increase in follicular B cell numbers and selective recovery of the MZ B cell compartment. Together these findings suggest that maintenance of the follicular and MZ B cell compartments require CD19-dependent survival signals.
ATP-Citrate Lyase Is Required for Production of Cytosolic Acetyl Coenzyme A and Development in Aspergillus nidulans (2010)

Acetyl coenzyme A (CoA) is a central metabolite in carbon and energy metabolism and in the biosynthesis of cellular molecules. A source of cytoplasmic acetyl-CoA is essential for the production of fatty acids and sterols and for protein acetylation, including histone acetylation in the nucleus. In Saccharomyces cerevisiae and Candida albicans acetyl-CoA is produced from acetate by cytoplasmic acetyl-CoA synthetase, while in plants and animals acetyl-CoA is derived from citrate via ATP-citrate lyase. In the filamentous ascomycete Aspergillus nidulans, tandem divergently transcribed genes (aclA and aclB) encode the subunits of ATP-citrate lyase, and we have deleted these genes. Growth is greatly diminished on carbon sources that do not result in cytoplasmic acetyl-CoA, such as glucose and proline, while growth is not affected on carbon sources that result in the production of cytoplasmic acetyl-CoA, such as acetate and ethanol. Addition of acetate restores growth on glucose or proline, and this is dependent on facA, which encodes cytoplasmic acetyl-CoA synthetase, but not on the regulatory gene facB. Transcription of aclA and aclB is repressed by growth on acetate or ethanol. Loss of ATP-citrate lyase results in severe developmental effects, with the production of asexual spores (conidia) being greatly reduced and a complete absence of sexual development. This is in contrast to Sordaria macrospora, in which fruiting body formation is initiated but maturation is defective in an ATP-citrate lyase mutant. Addition of acetate does not repair these defects, indicating a specific requirement for high levels of cytoplasmic acetyl-CoA during differentiation. Complementation in heterokaryons between aclA and aclB deletions for all phenotypes indicates that the tandem gene arrangement is not essential.
A Synthesis of DL-Proline (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Synthesis of DL-ProlineNoel F. Albertson and Jeanne L. FillmanCite this: J. Am. Chem. Soc. 1949, 71, 8, 2818–2820Publication Date (Print):August 1, 1949Publication History Published online1 May 2002Published inissue 1 August 1949https://pubs.acs.org/doi/10.1021/ja01176a065https://doi.org/10.1021/ja01176a065research-articleACS PublicationsRequest reuse permissionsArticle Views740Altmetric-Citations23LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells (2013)

Mannan binding lectin (MBL)-associated serine protease type 1 (MASP-1) has a central role in the lectin pathway of complement activation and is required for the formation of C3 convertase. The activity of MASP-1 in the peripheral blood has been identified previously as a highly significant predictor of the severity of liver fibrosis in hepatitis C virus (HCV) infection, but not in liver disease of other aetiologies. In this study we tested the hypotheses that expression of MASP-1 may promote disease progression in HCV disease by direct activation of hepatic stellate cells (HSCs) and may additionally be up-regulated by HCV. In order to do so, we utilized a model for the maintenance of primary human HSC in the quiescent state by culture on basement membrane substrate prior to stimulation. In comparison to controls, recombinant MASP-1 stimulated quiescent human HSCs to differentiate to the activated state as assessed by both morphology and up-regulation of HSC activation markers α-smooth muscle actin and tissue inhibitor of metalloproteinase 1. Further, the expression of MASP-1 was up-regulated significantly by HCV infection in hepatocyte cell lines. These observations suggest a new role for MASP-1 and provide a possible mechanistic link between high levels of MASP-1 and the severity of disease in HCV infection. Taken together with previous clinical observations, our new findings suggest that the balance of MASP-1 activity may be proinflammatory and act to accelerate fibrosis progression in HCV liver disease.