gebhart/patrepeval huggingface dataset:
Plasminogen Activator Inhibitor-1 Is a Major Determinant of Arterial Thrombolysis Resistance (1999)

Background —Platelet-rich thrombi are resistant to lysis by tissue plasminogen activator (tPA). Plasminogen activator inhibitor-1 (PAI-1), a rapid inhibitor of tPA, may contribute to arterial thrombolysis resistance. However, few data are available regarding the effect of PAI-1 on arterial thrombolysis in animals. We used a murine carotid injury model to test the hypothesis that PAI-1 inhibits thrombolysis mediated by pharmacological concentrations of tPA. Methods and Results —Platelet-rich thrombi were induced in wild-type mice ( PAI-1 +/+; n=11) and PAI-1–deficient mice ( PAI-1 −/−; n=11) with ferric chloride. Baseline carotid blood flows and mean occlusion times did not differ between PAI-1 +/+ and PAI-1 −/− mice. Clot lysis was induced by infusion of heparin (200 U/kg bolus, 70 U · kg −1 · h −1 drip), human plasminogen (50 mg/kg), and tPA at 20 (n=10) or 100 (n=12) μg · kg −1 · min −1 . Mean plasma tPA antigens were 2.7 μg/mL (tPA infusion, 20 μg · kg −1 · min −1 ) and 5.5 μg/mL (tPA infusion, 100 μg · kg −1 · min −1 ), with no significant differences between PAI-1 +/+ mice and PAI-1 −/− mice. Reperfusion after tPA 20 μg · kg −1 · min −1 occurred in 1 of 5 PAI-1 +/+ mice versus 5 of 5 PAI-1 −/− mice ( P =0.0006). Reperfusion occurred in all mice that received tPA 100 μg · kg −1 · min −1 , but reperfusion times were significantly shorter in PAI-1 −/− mice (17.8±2.6 minutes, n=6) than in PAI-1 +/+ mice (35.7±5.1 minute, n=6; P =0.01). Histological analyses confirmed that carotid thrombi were platelet rich and that PAI-1 was distributed uniformly throughout thrombi from PAI-1 +/+ mice. Lysates of PAI-1 +/+ platelets inhibited human tPA, whereas PAI-1 −/− platelet lysates did not. Conclusions —PAI-1 is a major determinant of the resistance of platelet-rich arterial thrombi to lysis by pharmacological concentrations of tPA. Strategies to inhibit or resist PAI-1 may enhance thrombolysis.
M. paratuberculosisHeat Shock Protein 65 and Human Diseases: Bridging Infection and Autoimmunity (2012)

Mycobacterium avium subspecies paratuberculosis (MAP) is the known infectious cause of Johne's disease, an enteric inflammatory disease mostly studied in ruminant animals. MAP has also been implicated in the very similar Crohn's disease of humans as well as sarcoidosis. Recently, MAP has been associated with juvenile sarcoidosis (Blau syndrome), autoimmune diabetes, autoimmune thyroiditis, and multiple sclerosis. While it is intuitive to implicate MAP in granulomatous diseases where the microbe participates in the granuloma, it is more difficult to assign a role for MAP in diseases where autoantibodies are a primary feature. MAP may trigger autoimmune antibodies via its heat shock proteins. Mycobacterial heat shock protein 65 (HSP65) is an immunodominant protein that shares sequential and conformational elements with several human host proteins. This molecular mimicry is the proposed etiopathology by which MAP stimulates autoantibodies associated with autoimmune (type 1) diabetes, autoimmune (Hashimoto's) thyroiditis, and multiple sclerosis. This paper proposes that MAP is a source of mycobacterial HSP65 and acts as a trigger of autoimmune disease.
Partial characterization of specific inducers of a cuticle-degrading protease from the insect pathogenic fungus Metarhizium anisopliae (1994)

The insect pathogenic fungus Metarhizium anisopliae produces several extracellular cuticle-degrading proteases and evidence is consistent with one of these, PR1, which is a chymoelastase, being a determinant of pathogenicity. We have shown previously that PR1 production is regulated by both carbon catabolite and nitrogen metabolite repression and also by specific induction under derepressed conditions by insect cuticle. In the present work we have established that an enzymically released proteinaceous component(s) of insect cuticle is capable of inducing PR1 (based on appearance of extracellular activity). Cuticle of the desert locust Schistocerca gregaria treated with KOH to remove protein failed to induce PR1 production, whereas cuticle treated with either chloroform or ether to remove lipids still induced PR1. Cuticle digested with either PR1 or the trypsin-like PR2 of M. anisopliae released peptides mainly in the range 150-2000 Da; addition of these peptides generated by PR1 or PR2 at 3 micrograms alanine equivalents ml-1 induced PR1 production to a level similar (75%) to that obtained with untreated insect cuticle. Several amino acids and peptides which are abundant in insect cuticular protein (Ala, Gly, Ala-Ala, Ala-Ala-Ala, Ala-Pro and Pro-Ala) were tested at a range of concentrations and in restricted cultures for their ability to induce PR1. None induced the protease to the levels seen with cuticle or peptides enzymically released from cuticle, although some dimers and notably the monomers Ala and Gly gave 2-2.7-fold enhanced PR1 activity above depressed basal levels (up to 48-57% of that achieved with induced synthesis on cuticle).(ABSTRACT TRUNCATED AT 250 WORDS)
PI3K Signaling in Glioma—Animal Models and Therapeutic Challenges (2008)

The PI3 kinase (PI3K) family plays a complex role in cell biology and metabolism. Signaling through the PI3Ks is frequently activated in many human cancers, including glioblastoma, because of gain-of-function mutations in PIK3CA or loss of PTEN. Experiments involving genetic mouse models and small molecule inhibitors have helped to elucidate the roles of the regulatory and catalytic subunits of PI3K in metabolism and cancer. Downstream of PI3K is Akt, a critical effector of growth, proliferation and survival. The suggested dependence of glioblastoma tumors on PI3K signaling implies that PI3K inhibitors should lead to effective killing of these cancer cells, but that has been shown not to be the case. The engagement of other survival pathways in response to PI3K inhibition prompts the need to develop combination therapies that promote cytotoxicity in cancer cells.
Verifiable Partial Key Escrow. (1996)

One of the main objections to existing proposals for key escrow is that the individual&amp;apos;s privacy relies on too high a level of trust in the law enforcement agencies. In particular, even if the government is trustworthy today, it may be replaced by an un-trustworthy government tomorrow which could immediately and suddenly recover the secret keys of all users. &amp;quot;Partial key escrow&amp;quot; was suggested to address this concern, in the context of DES keys. Only some part of a user key is escrowed, so that the authority must make a computational effort to find the rest. We extend this idea and provide schemes to perform partial key escrow in a verifiable manner in a public-key encryption setting. We uncover some subtle issues which must be addressed for any partial key escrow scheme to be secure, the most important of which is the danger of early recovery. We show that other proposals for verifiable partial key escrow suffer from the early recovery problem, and thus do not in fact offer an advantage over standard key-escrow schemes. Our verifiable partial key escrow scheme for the Diffie-Hellman cryptosystem does not suffer from early recovery. Political debate will not make the user versus law-enforcement conflict on privacy vanish. Today we are seeing corporations, pushed by their business needs, ready to accept some form of key escrow. The realistic and urgent question is to find the form which guarantees the most privacy. Our schemes are candidates.
Immunostimulatory Oligonucleotides Attenuate Airways Remodeling in Allergic Monkeys (2004)

To determine whether inhaled immunostimulatory DNA sequence oligonucleotides containing CpG motifs mitigate the pathophysiologic manifestation of the asthmatic phenotype (airways hyperresponsiveness and airways remodeling), rhesus monkeys with experimentally induced allergic airways disease were treated seven times with inhaled immunostimulatory oligonucleotides (or sham) periodically for 33 weeks. Airways hyperresponsiveness was reduced twofold in immunostimulatory DNA sequence-treated compared with sham-treated monkeys. Airways from immunostimulatory oligonucleotide-treated monkeys had thinner reticular basement membranes, fewer mucous cells, fewer eosinophils, and fewer mast cells than sham-treated allergic monkeys. We conclude that inhaled immunostimulatory oligonucleotides can attenuate the magnitude of airway hyperreactivity and airways remodeling produced in nonhuman primates with experimentally induced allergic airways disease.
Molecular assembly of plasminogen and tissue‐type plasminogen activator on an evolving fibrin surface (1993)

A well characterized model of an intact and a degraded surface of fibrin that represents the states of fibrin during the initiation and the progression of fibrinolysis was used to quantitatively characterize the molecular interplay between tissue-type plasminogen activator (t-PA), plasminogen and fibrin. The molecular assembly of t-PA and plasminogen on these surfaces was investigated using combinations of proteins that preclude complications due to side reactions caused by generated plasmin: native plasminogen with di-isopropylphosphofluoridate-inactivated t-PA, and a recombinant human plasminogen with the active-site Ser741 mutagenized to Ala which renders the catalytic site inactive. Under these conditions, neither the affinity nor the maximal number of binding sites for plasminogen were modified by the presence of t-PA, indicating that binding sites for plasminogen pre-exist in intact fibrin and are not dependent on the presence of t-PA. In contrast, when plasminogen activation is allowed, increasing binding of plasminogen to the progressively degraded fibrin surface is directly correlated (r = 0.98) to the appearance of the fibrin E-fragment as shown using a monoclonal antibody (FDP-14) that has its epitope in the E domain of fibrin. t-PA was shown to bind with a high affinity to both the intact (Kd = 3.3 +/- 0.6 nM) and the degraded surface of fibrin (Kd = 1.2 +/- 0.4 nM). Binding of t-PA to carboxy-terminal lysine residues of degraded fibrin was shown to be efficiently competed by physiological concentrations of plasminogen (2 microM), indicating that the affinity of t-PA for these residues was lower than that of plasminogen (Kd = 0.66 +/- 0.22 microM) and unrelated to the high affinity of t-PA for specific binding sites on intact fibrin. These data confirm and establish that the generation of carboxy-terminal lysine residues on fibrin during ongoing fibrinolysis, and the binding of plasminogen to these sites, is an important pathway in the acceleration of clot dissolution.
Inactivated influenza virus, when presented on dendritic cells, elicits human CD8+ cytolytic T cell responses. (1995)

Inactivated or subunit virus preparations have been excellent vaccines for inducing antibody responses. Generation of cytolytic T cell responses, however, is thought to require replicating virus, primarily to provide sufficiently large amounts of cytoplasmic proteins for processing and presentation on major histocompatibility complex class I molecules by antigen-presenting cells. Potent human CD8+ cytolytic T cell responses to live replicating influenza A virus are generated when dendritic cells are used as the antigen-presenting cells. Here, we demonstrate that dendritic cells pulsed with poorly replicating, heat- or ultraviolet-inactivated influenza virus, induce equally strong CD8+ cytolytic T lymphocyte responses. The cytotoxic T lymphocytes are generated in the apparent absence of CD4+ helper cells or exogenous cytokines. Active viral protein synthesis is not required to charge class I molecules on dendritic cells. When pulsed with inactivated virus, < 1% of dendritic cells express nonstructural protein 1, which is only synthesized in the infectious cycle. To be optimally effective, however, the inactivated virus must retain its fusogenic activity, and presumably access the cytoplasm of dendritic cells. The data indicate, therefore, that dendritic cells require only small amounts of viral protein to charge class I molecules, most likely via traditional class I processing pathways. These results reopen the potential use of inactivated virus preparations as immunogens for cytotoxic T lymphocyte responses.
Glyphosate‐Resistant Soybean Cultivar Yields Compared with Sister Lines (2001)

Herbicide‐resistant crops like glyphosate resistant (GR) soybean [ Glycine max (L.) Merr.] are gaining acceptance in U.S. cropping systems. Comparisons from cultivar performance trials suggest a yield suppression may exist with GR soybean. Yield suppressions may result from either cultivar genetic differentials, the GR gene/gene insertion process, or glyphosate. Grain yield of GR is probably not affected by glyphosate. Yield suppression due to the GR gene or its insertion process (GR effect) has not been reported. We conducted a field experiment at four Nebraska locations in 2 yr to evaluate the GR effect on soybean yield. Five backcross‐derived pairs of GR and non‐GR soybean sister lines were compared along with three high‐yield, nonherbicide‐resistant cultivars and five other herbicide‐resistant cultivars. Glyphosate resistant sister lines yielded 5% (200 kg ha −1 ) less than the non‐GR sisters (GR effect). Seed weight of the non‐GR sisters was greater than that of the GR sisters (in 1999) and the non‐GR sister lines were 20 mm shorter than the GR sisters. Other variables monitored were similar between the two cultivar groups. The high‐yield, nonherbicide‐resistant cultivars included for comparison yielded 5% more than the non‐GR sisters and 10% more than the GR sisters.
On the pressure dependence of the positive column cross section in high-pressure glow discharges (2001)

The cross section and the current density at the two ends of a positive column, measured as functions of pressure, were found to be different in glow discharges operated between copper electrodes in air, nitrogen and helium in the pressure range of 100-760 Torr and at an electrode distance of 7 mm. Taking into consideration the occurrence of the dissociative recombination of positive molecular ions, the observed difference is explained by the different pressure dependences and magnitudes of the cathode and anode falls, which determine the current densities at these places.
Immunopurification of Pathological Prion Protein Aggregates (2009)

The immunopurification protocol described here isolates biologically active forms of aggregated PrP. These preparations may be useful for investigating the structural and chemico-physical properties of infectious and neurotoxic PrP aggregates.
Fine-grained sleep transistor sizing algorithm for leakage power minimization (2007)

Power gating is one of the most effective ways to reduce leakage power. In this paper, we introduce a new relationship among Maximum Instantaneous Current, IR drops and sleep transistor networks from a temporal viewpoint. Based on this relationship, we propose an algorithm to reduce the total sizes of sleep transistors in Distributed Sleep Transistor Network designs. On average, the proposed method can achieve 21% reduction in the sleep transistor size.
Aberrant production of interleukin-8 and thrombospondin-1 by psoriatic keratinocytes mediates angiogenesis. (1994)

Psoriasis is a common inherited skin disease that is characterized by hyperproliferation of epidermal keratinocytes and excessive dermal angiogenesis. A growing body of evidence supports a key pathogenetic role for activated keratinocytes in the angiogenic response that accompanies psoriasis. We investigated the role of psoriatic epidermis in the aberrant expression of angiogenesis by examining the ability of pure populations of multipassaged keratinocytes obtained from the skin of normal individuals and psoriatic patients to induce angiogenesis in vivo in the rat corneal bioassay and endothelial cell chemotaxis in vitro. Media conditioned by keratinocytes from psoriatic patients, including both symptomless skin and psoriatic plaques, induced vigorous angiogenic responses in over 90% of corneas tested and potently stimulated directional migration of capillary endothelial cells in vitro. In contrast, conditioned medium from normal keratinocyte cultures was weakly positive in less than 10% of corneas assayed and failed to stimulate endothelial cell chemotaxis. Furthermore, keratinocytes from psoriatic skin exhibited a 10- to 20-fold increase in interleukin-8 production and a seven-fold reduction in thrombospondin-1 production. The angiogenic activity present in keratinocyte-conditioned media from psoriatic patients was suppressed by adding either highly purified thrombospondin-1 (125 ng) or following the addition of either normal keratinocyte-conditioned media or neutralizing interleukin-8 antibody. We conclude that psoriatic keratinocytes are phenotypically different from normal keratinocytes with respect to their angiogenic capacity and that this aberrant phenotype is attributable to a defect in the overproduction of interleukin-8 and a deficiency in the production of the angiogenesis inhibitor thrombospondin-1.
The use of umbilical cord blood in mismatched related and unrelated hemopoietic stem cell transplantation. (1994)

Over the past 6 years, umbilical cord blood has emerged as an efficacious alternative source of hematopoietic stem cells in related bone marrow transplantation. These encouraging results led us to extend this technology to the mismatched related and unrelated settings in three high-risk leukemic children lacking a matched-related donor for transplantation. Two of the three children also lacked identifiable donors through the National Marrow Donor Program, while the third was in relapse and did not have time to wait for completion of a search. The first child was transplanted with haploidentical umbilical cord blood-derived mononuclear cells from his sister, while the remaining two children were transplanted with partially mismatched, unseparated, unrelated umbilical cord blood banked through the Placental Blood Project at the New York Blood Center. All three children demonstrated trilineage engraftment with donor cells within 6 weeks of transplantation. The patient transplanted with haploidentical marrow developed grade 2 graft vs. host disease (GVHD), which was controlled with steroid and anti-thymocyte globulin (ATG) therapy. One of the two patients grafted with unrelated umbilical cord blood developed mild grade 1 GVHD of the skin, which rapidly cleared with steroid therapy. One patient remains alive, in good health and disease-free 12 months from transplantation.
Mechanism and kinetics of ordering in diblock copolymer thin films on chemically nanopatterned substrates (2005)

Abstract Lamellae forming diblock copolymer domains can be directed to assemble without defects and in registration with chemically nanopatterned substrates. Initially, thin films of the lamellar poly(styrene‐ b ‐methyl methacrylate) block copolymer form hexagonally close‐packed styrene domains when annealed on chemical nanopatterned striped surfaces. These styrene domains then coalesce to form linear styrene domains that are not fully registered with the underlying chemical surface pattern. Defects coarsen, until defect‐free directed assembly is obtained, by breaking linear styrene domains and reforming new structures until registered lamellae have been formed. At all stages in the process, two factors play an important role in the observed degree of registration of the block copolymer domains as a function of annealing time: the interfacial energy between the blocks of the copolymer and the chemically nanopatterned substrate and the commensurability of the bulk repeat period of the block copolymer and the substrate pattern period. Insight into the time‐dependent three‐dimensional behavior of the block copolymer structures is gained from single chain in mean field simulations. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3444–3459, 2005
Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles (1999)

We have performed a real time analysis of fluorescence-tagged vesicle and mitochondria movement in living CHO cells transfected with microtubule-associated protein tau or its microtubule-binding domain. tau does not alter the speed of moving vesicles, but it affects the frequencies of attachment and detachment to the microtubule tracks. Thus, tau decreases the run lengths both for plus-end and minus-end directed motion to an equal extent. Reversals from minus-end to plus-end directed movement of single vesicles are strongly reduced by tau, but reversals in the opposite direction (plus to minus) are not. Analogous effects are observed with the transport of mitochondria and even with that of vimentin intermediate filaments. The net effect is a directional bias in the minus-end direction of microtubules which leads to the retraction of mitochondria or vimentin IFs towards the cell center. The data suggest that tau can control intracellular trafficking by affecting the attachment and detachment cycle of the motors, in particular by reducing the attachment of kinesin to microtubules, whereas the movement itself is unaffected.
Expression of Sox-9 in Metastatic Melanoma-A Potential Diagnostic Pitfall (2010)

SOX-9 was originally identified as a master regulator gene that plays a role in the differentiation of mesenchymal cells to chondrocytes. Since then, SOX-9 has been implicated in neural crest development and has emerged as a transcriptional regulator of melanogenesis. Because the role of immunohistochemical detection of SOX-9 in the routine diagnosis of melanoma has not been previously described, we attempted to elucidate the spectrum and labeling characteristics of this antibody in a large cohort of patients with metastatic melanoma. We analyzed the expression of SOX-9 on sections of metastatic melanoma in a tissue microarray and compared the expression of this marker with 3 commonly used melanocytic markers (MART-1, HMB-45 antigen, and S-100 protein). SOX-9 expression was noted in 52 of the 62 cases (83.9%). In comparison, HMB-45 was positive in 53 of the 62 cases (85.5%), MART-1 was positive in 59 of the 62 cases (95.1%), and S-100 protein was positive in 57 of the 62 cases (95%). Interestingly, there were 5 tumors that were negative for 2 or more markers while being positive for SOX-9. Furthermore, 3 of these were negative for all markers except for SOX-9. Our study illustrates that SOX-9 is expressed in a high percentage of melanomas. Furthermore, SOX-9 may be a useful adjunct in the work-up of metastatic melanoma, in such cases where the tumor is negative for the other commonly used melanocytic markers. Last, our data confirm that SOX-9 is not a specific marker for tumors of cartilage lineage and may be expressed in other tumors of neural crest origin.