gebhart/patrepeval huggingface dataset:
3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models (2012)

The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.
Human pediatric and adult ventricular cardiomyocytes in culture: assessment of phenotypic changes with passaging (1996)

Primary cultures of human pediatric and adult partially differentiated ventricular cardiomyocytes can be passaged. Although rapid disorganization of the myofibrils occurs, the non-contractile cells can be identified as cardiomyocytes by morphological appearance, immunofluorescent staining, Northern blot analysis for HVMHC, and CK-MB activity.
The transputer (1985)

The transputer is a programmable VLSI component with communication links for point-to-point connection to other transputers. Occam (*) is a language that enables a multi-transputer system to be described as a collection of processes that ogerate concurrently and communicate using message passing via named channels.
Crystal structure of a clavaminate synthase–Fe(II)–2‐oxoglutarate–substrate–NO complex: evidence for metal centred rearrangements (2002)

Clavaminate synthase (CAS), a 2-oxoglutarate (2OG) dependent dioxygenase, catalyses three steps in the biosynthesis of clavulanic acid. Crystals of CAS complexed with Fe(II), 2OG and deoxyguanidinoproclavaminate were exposed to nitric oxide (NO) acting as a dioxygen analogue. Prior to exposure with NO, the active site Fe(II) is octahedrally coordinated by a water molecule, the 2-oxo and 1-carboxylate groups of 2OG, and the side-chains of an aspartyl and two histidinyl residues. NO binds to the position previously occupied by the 2OG 1-carboxylate concomitant with rearrangement of the latter to the position previously occupied by the displaced water.
Abstract 5145: Y-27632 inhibits Myc-induced apoptosis and cooperates with Myc to immortalize human keratinocytes (2015)

Abstract The high-risk HPV E6 and E7 genes are sufficient to immortalize human foreskin keratinocytes (HFKs) through activation of telomerase and inactivation of the RB/p16 pathway, respectively. Our previous work has shown that Myc (via induction of hTERT) may substitute for E6 and immortalize HFKs when combined with HPV E7. When expressed alone, however, Myc induced p53 expression and apoptosis. In the current study we found that Myc, in combination with the ROCK inhibitor (Y-27632), led immortalization of human foreskin keratinocytes. Our data confirmed that Myc induced apoptosis and blebbing of human keratinocytes when cultured in serum free synthetic medium (KGM) and that Y-27632 rapidly inhibits this process. Thus, our data demonstrate that Myc is capable of independently immortalizing HFKs when apoptosis pathways are blocked. Citation Format: Aleksandra Dakic, Kyle Divito, Shuang Fang, Nancy Palechor-Ceron, Vera Simic, Sujata Choudhury, Songtao Yu, Cynthia M. Simbulan-Rosenthal, Dean Rosenthal, Richard Schlegel, Xuefeng Liu. Y-27632 inhibits Myc-induced apoptosis and cooperates with Myc to immortalize human keratinocytes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5145. doi:10.1158/1538-7445.AM2015-5145
Developing business object models with patterns and ontologies (2005)

We propose a new approach for developing Business Object Model (BOMs). The approach uses ontologies to unify the representation and integration of knowledge from analysis patterns with different structures.
A Synthetic Peptide Containing the IKVAV Sequence from the A Chain of Laminin Mediates Cell Attachment, Migration, and Neurite Outgrowth (1989)

Laminin is a basement membrane glycoprotein which consists of A, B1, and B2 chains. Laminin has diverse biological activities including promoting cell adhesion, migration, differentiation, growth, and neurite extension. Synthetic peptides from the active region of the A chain were prepared and tested for their biological activity. A 19-mer peptide (designated PA22-2), from just above the carboxyl globule on the long arm of the A chain, was found to promote cell adhesion, spreading, migration, and neurite outgrowth. By testing smaller sequences within the 19-mer peptide, a constituent pentapeptide, IKVAV (Ile-Lys-Val-Ala-Val), was identified as the active site for cell adhesion and neurite outgrowth. These data suggest that this sequence is one of the principle sites in laminin which regulate cellular behavior.
The mechanism of the Cannizzaro reaction of Formaldehyde (1954)

For a wide range of concentrations of formaldehyde and alkali, the Cannizzaro reaction of formaldehyde can be described as the sum of a third and a fourth order reaction. However, the concentrations which are used for the rate equations must be corrected for the amount of methylene glycol anion present. The dissociation constant of methylene glycol as determined from the kinetic data is the same magnitude as that derived electrometrically. The mechanism of the reaction is interpreted as a reaction between formaldehyde and the hydride ion donors CH2(O-)(OH) and CH2(O-)(O-) It is shown why the third order reaction proposed by previous workers is not always applicable.
PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer (2015)

Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor-immune interface. These lymph node metastases persist for years, generally without progression to distant metastases. Although the immune system likely impedes disease progression, it is unsuccessful in eliminating disease. Our previous studies revealed that programmed death-1 (PD-1)(+) T cells were enriched in tumor-involved lymph nodes (TILN). Tumor-associated leukocytes and tumor cells were collected from grossly involved lymph nodes from 12 patients to further characterize the phenotype and functional potential of mDTC-associated PD-1(+) T cells. PD-1(+)CD4(+) and PD-1(+)CD8(+) T cells were enriched in 8 of 12 TILN samples. PD-1(+) T cells coexpressed Tim-3 and CD69 and failed to downregulate CD27. CD8(+) T cells, but not CD4(+) T cells, from these samples were variably deficient in their ability to produce effector cytokines when compared with control TILNs that lacked resident PD-1(+) T cells. PD-1(+)CD8(+) T cells were capable of exocytosis but lacked intracellular perforin. Surprisingly, T-cell proliferative capacity was largely maintained in all samples. Thus, although PD-1 expression by mDTC-associated CD8(+) T cells was associated with dysfunction, exhaustion was not complete. Notably, molecular markers of exhaustion did not translate to dysfunction in all samples or in CD4(+) T cells. Regulatory T cells (Treg), PD-L1, and galectin-9 were commonly found in mDTC and likely contributed to the initiation of T-cell exhaustion and disease progression. Therapies that release the effects of PD-1 and Tim-3 and reduce the suppressive effects of Tregs may encourage tumor elimination in patients with mDTC.
hOLF44, a secreted glycoprotein with distinct expression pattern, belongs to an uncharacterized olfactomedin‐like subfamily newly identified by phylogenetic analysis (2004)

Secreted proteins are indispensable for the development and differentiation of multicellular organisms. Cloning and characterization of novel or hypothetical genes encoding these proteins are therefore inviting great incentives. Using bioinformatics tools and experimental approaches, we isolated and characterized a human secreted glycoprotein, hOLF44, which contains a highly conserved olfactomedin-like (OLF) domain in the C-terminal. However, phylogenetic analysis revealed that hOLF44 is not clustered into any of the OLF subfamilies containing characterized members, and obviously falls into a newly identified uncharacterized OLF subfamily. Western blot analysis showed that hOLF44 protein is robustly secreted from the transfected COS-7 cells. Expression levels of hOLF44 mRNA are abundant in placenta, moderate in liver and heart, whereas fairly weak in other tissues examined. Immunohistochemical study on human term placenta demonstrated that hOLF44 is mainly localized extracellularly surrounding the syncytiotrophoblastic cells and very rarely expressed in the maternal decidua layer. These results suggest that hOLF44 may have matrix-related function involved in human placental and embryonic development, or play a similar role in other physiological processes. The further functional characterization of hOLF44 may provide insights into a better understanding of the newly identified OLF subfamily.
Antibody response to low-molecular-weight antigens of Aspergillus fumigatus in allergic bronchopulmonary aspergillosis (1989)

Sera from patients with allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma and normal sera were analyzed for specific antibodies by Western (immuno-) blotting with Aspergillus fumigatus antigens transferred electrophoretically onto polyvinylidene difluoride membranes. Western blot analysis demonstrated consistent reactivity of low-molecular-weight A. fumigatus antigens against ABPA sera but not against uncomplicated aspergilloma or normal sera. None of these low-molecular-weight components had any lectin-binding activity. Sera from patients with aspergilloma, however, frequently reacted with high-molecular-weight components of A. fumigatus. The majority of these high-molecular-weight antigenic components demonstrated concanavalin A-binding activity. The low-molecular-weight bands were discernible in Western blots with sera from all ABPA patients irrespective of disease activities, such as relapse, flare, or treatment. Antibodies detected by methods such as immunodiffusion or enzyme-linked immunosorbent assays demonstrated total antibody responses to most or all antigenic components, while Western blots demonstrated the reactivities of the individual components with the specific antibodies. Western blot analysis thus provided more information for immunodiagnosis of ABPA than other methods, especially when only crude antigens were available.
Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials. (1994)

Previously we have shown that high metastatic colonic carcinoma cells express relatively more lamp molecules and sialyl Le(x) structures on the cell surface than their corresponding low metastatic counterparts (Saitoh, O., Wang, W.-L., Lotan, R., and Fukuda, M. (1992) J. Biol. Chem. 267, 5700-5711). In the present study, we extended these findings by testing whether these high and low metastatic colonic carcinoma cells differ in their adhesion efficiency to E-selectin-expressing cells. First, it was found that the high metastatic cells, as compared to their low metastatic counterparts, bind more efficiently to activated human endothelial cells that express E-selectin. This was also true when the adhesion was tested for Chinese hamster ovary cells stably expressing E-selectin. In addition, it was found that the high metastatic cells also adhere more efficiently to mouse endothelioma cells after activation with interleukin-1 beta. It was also shown that the adhesion can be inhibited by soluble lamp-1 or soluble leukosialin that contain sialy Le(x) termini. The inhibition was not, however, observed when these soluble glycoproteins lack sialyl Le(x) structures. The results indicate that the efficiency of the E-selectin-mediated binding of colonic carcinoma cells to human and mouse endothelial cells correlates with the metastatic potential of the cells and suggest that this adhesive event may be one of the critical factors for the metastatic spread of tumor cells. Soluble forms of leukosialin or lamp-1 may be useful as therapeutic agents for the inhibition of E-selectin-mediated binding to tumor cells.
Acetazolamide in the Treatment of Acute Mania (1998)

Several antiepileptic drugs are also being used in affective disorders. There are some hints that also the carbonic anhydrase inhibitor acetazolamide might be useful in the treatment of bipolar affective disorder. We report a 39-year-old male patient with a history of bipolar affective disorder who presented with his second manic episode. Acetazolamide was added to a low dose of valproic acid and to perazine. A marked decrease of the BRMAS score was achieved. The implications of this case are discussed.
The Myelin-Associated Oligodendrocytic Basic Protein Region MOBP15–36 Encompasses the Immunodominant Major Encephalitogenic Epitope(s) for SJL/J Mice and Predicted Epitope(s) for Multiple Sclerosis-Associated HLA-DRB1*1501 (2004)

Autoimmune response to the myelin-associated oligodendrocytic basic protein (MOBP), a CNS-specific myelin constituent, was recently suggested to play a role in the pathogenesis of multiple sclerosis (MS). The pathogenic autoimmune response to MOBP and the associated pathology in the CNS have not yet been fully investigated. In this study, we have characterized the clinical manifestations, pathology, T cell epitope-specificity, and TCRs associated with experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with recombinant mouse MOBP (long isoform, 170 aa). Analysis of encephalitogenic MOBP-reactive T cells for reactivity to overlapping MOBP peptides defined MOBP15-36 as their major immunodominant epitope. Accordingly, MOBP15-36 was demonstrated to be the major encephalitogenic MOBP epitope for SJL/J mice, inducing severe/chronic clinical EAE associated with intense perivascular and parenchymal infiltrations, widespread demyelination, axonal loss, and remarkable optic neuritis. Molecular modeling of the interaction of I-A(s) with MOBP15-36, together with analysis of the MOBP15-36-specific T cell response to truncated peptides, suggests MOBP20-28 as the core sequence for I-A(s)-restricted recognition of the encephalitogenic region MOBP15-36. Although highly focused in their epitope specificity, the encephalitogenic MOBP-reactive T cells displayed a widespread usage of TCR Vbeta genes. These results would therefore favor epitope-directed, rather than TCR-targeted, approaches to therapy of MOBP-associated pathogenic autoimmunity. Localization by molecular modeling of a potential HLA-DRB1*1501-associated MOBP epitope within the encephalitogenic MOBP15-36 sequence suggests the potential relevance of T cell reactivity against MOBP15-36 to MS. The reactivity to MOBP15-36 detected in MS shown here and in another study further emphasizes the potential significance of this epitope for MS.
Wafer‐Scale Fabrication of Ordered Binary Colloidal Monolayers with Adjustable Stoichiometries (2011)

Abstract Colloidal monolayers with high order and increased complexity beyond plain hexagonal packing geometries are useful for 2D templating of surface nanostructures and lithographic applications. Here, binary colloidal monolayers featuring a close‐packed monolayer of large spheres (L) with a superlattice of small particles (S) are prepared in a single step using a Langmuir trough. Adjustment of the stoichiometry of the two particle types at the air–water interface leads to a high degree of control over the occupation of the interstitial sites in the close‐packed layer of large spheres by the small colloids. Thus, large areas of binary 2D crystals with LS 2 , LS 6 , and LS 9 structures are fabricated in a controlled way. The process allows the formation of binary crystals over a wide range of particle size ratios from 0.19 to 0.40. The pH value of the subphase can be used to enhance the crystallization process by changing the contact angle of the particles at the interface. An interfacial polymerization of butyl cyanoacrylate is used to directly image the contact angle of the colloids at the interface. Transfer to solid substrates is achieved by a surface lowering technique. A variety of substrates with arbitrary topographies can thus be decorated with colloidal monolayers. Applied to a lithographic process, such monolayer architectures allow the generation of complex patterns, not accessible with conventional close‐packed monolayers.
Validation of a new prognostic index for patients with chronic lymphocytic leukemia (2008)

The results of the current study confirm the ability of a newly developed prognostic index to predict survival among patients with previously untreated CLL. The study also extended the utility of the index by demonstrating that it is useful at diagnosis, retains prognostic value when applied exclusively to Rai stage 0 patients, is effective in nonreferred patients, and predicts time to treatment.
In Vivo Activation of Human NK Cells by Treatment with an Interleukin-15 Superagonist Potently Inhibits Acute In Vivo HIV-1 Infection in Humanized Mice (2015)

Epidemiological studies have indicated that NK cells contribute to the control of HIV-1 infection, and in vitro studies have demonstrated that NK cells can selectively kill HIV-1-infected cells. We demonstrated that in vivo activation of NK cells by treatment with an IL-15 superagonist that potently stimulates the antitumor activity of NK cells markedly inhibited acute HIV-1 infection in humanized mice, even when activation of NK cells by IL-15 superagonist treatment is delayed until 3 days after HIV-1 inoculation. NK cell depletion from PBMCs prior to their intrasplenic injection abrogated the suppression of in vivo HIV-1 infection observed in humanized mice treated with the IL-15 superagonist, demonstrating that activated human NK cells were mediating IL-15 superagonist-induced inhibition of acute HIV-1 infection. Thus, in vivo immunostimulation of NK cells, a promising therapeutic approach for cancer therapy, may represent a new treatment modality for HIV-1-infected individuals, particularly in the earliest stages of infection.
PHOTO‐CIDNP AS A TOOL FOR THE STUDY OF THE REACTIVITY OF PHOTOSENSITIZING DRUGS: THE FUROCOUMARINS (1988)

Abstract— Several monofunctional and bifunctional furocoumarin derivatives were studied by means of the photo‐CIDNP technique. Nuclear spin polarizations were observed on some of these derivatives when irradiated in acetonitrile solutions. The likely occurrence of both semi‐reduced and semi‐oxidized species of the FC in the reaction scheme is discussed. When N‐acetyltyrosine was added to the solution, CIDNP effects were observed on both reactants. They arose from a highly reversible pathway, as no photoproduct was polarized. On the FC part, the stronger effects were always observed on the 3,4 pyrone double bond suggesting that it must possess the highest spin density in the reaction intermediate. According to previous studies, the latter should be the FC anion or neutral radical. For the amino‐acid moiety, the intensity of the polarizations was strongly dependent on the nature of the FC. This allowed the classification of the FC into three groups (zero, weak and strong intensities). As compared with their photobiological reactivity, this classification seemed to be related to the usual mono‐ and bifunctional distinction. This is the second example showing that photo‐CIDNP could be used as a preliminary test for the study of the photosensitizing drug properties.
Novel antiplatelet strategies in acute coronary syndromes (2009)

Antiplatelet therapies for the treatment of acute coronary syndromes (ACS) act to interrupt various pathways of platelet activation. Clopidogrel, an established thienopyridine antiplatelet medication, inhibits adenosine diphosphate (ADP)-induced platelet aggregation to a modest degree and with wide variability in platelet response. Accumulating data suggest that a 600-mg loading dose of clopidogrel may help overcome the suboptimal response to the standard 300-mg dose seen in some patients. Prasugrel is a third-generation investigational thienopyridine that demonstrates more potent inhibition of platelet aggregation and more consistent platelet response compared with standard- and high-dose clopidogrel. A large clinical trial showed prasugrel to be superior to standard-dose clopidogrel in reducing ischemic events in patients with ACS scheduled for percutaneous coronary intervention, although prasugrel was associated with a significantly higher risk of major bleeding events. Other investigational antiplatelet agents also display more potent and consistent inhibition of platelet aggregation than is seen with clopidogrel. These include AZD6140, a reversible ADP receptor blocker; cangrelor, a rapidly acting intravenous ADP receptor blocker; and the thrombin receptor antagonist SCH 530348.
Structure and Function of Lipid-DNA Complexes for Gene Delivery (2000)

Owing to the rapid development of in vivo applications for nonviral gene delivery vectors, it is necessary to have a better understanding of how the structure-activity relationships of these lipid-DNA complexes are affected by their environment. Indeed, research in gene therapy first focused on in vitro cell culture studies to determine the mechanisms involved in the delivery of DNA into the cell. New biophysical techniques such as electron microscopy and X-ray diffraction have been developed to discern the structure of the lipid-DNA complex. However, further studies have revealed discrepancies between optimal lipid-DNA formulations for in vitro transfection and for in vivo administration of these vectors. Furthermore, some immune stimulatory effects have been associated with in vivo lipid-DNA administration. This review summarizes the current state of knowledge on in vitro and in vivo lipid-DNA complex transfections. New prospects of vectors for in vivo gene transfer are also discussed.
Gene therapy of rat C6 glioma using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene: long-term follow-up by magnetic resonance imaging. (1996)

The herpes simplex virus thymidine kinase gene was transferred into C6 glioma cells by infection with a recombinant adenovirus. In vitro, a 10 microM ganciclovir concentration was able to kill 100% of the infected cells. For in vivo experiments, brain tumors were established by stereotactic injection of C6 glioma cells in the caudate nucleus of rats. Five days later, the recombinant adenovirus was inoculated into the tumors and the animals were treated by intraperitoneal injections of ganciclovir for 14 days. At the end of ganciclovir therapy, histological examination revealed a 28-fold decrease in tumor volumes in the treated animals, as compared with control animals. In long-term studies, the mean survival time of the treated animals were four-fold longer than that of control ones. Magnetic resonance imaging demonstrated an apparent complete tumor regression in 62% of the animals. However, late tumor recurrence was observed in the treated animals. Repeated inoculation of C6 glioma cells in the contralateral hemisphere of long-term surviving animals resulted in either tumor rejection or slowly growing tumors. These findings demonstrate the potential efficacy of adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene and ganciclovir administration in the treatment of rat gliomas.
Probabilistic Name and Address Cleaning and Standardisation. (2002)

In the absence of a shared unique key, an ensemble of nonunique personal attributes such as names and addresses is often used to link data from disparate sources. Such data matching is widely used when assembling data warehouses and business mailing lists, and is a foundation of many longitudinal epidemiological and other health related studies. Unfortunately,