gebhart/patrepeval huggingface dataset:
Transgenic overexpression of the CC chemokine CCL21 disrupts T-cell migration (2001)

Chemokines are a large family of cytokines that direct normal leukocyte migration. They also have been implicated in leukocyte development and in the pathogenesis of many diseases. The CC chemokine CCL21, also known as Exodus-2, SLC, 6Ckine, and TCA4 induces both the adhesion and migration of human T cells. CCL21 is hypothesized to regulate the trafficking of T cells through secondary lymphoid tissues. To test this hypothesis, a transgenic mouse model was generated that placed the expression of mouse CCL21 (mCCL21) under the control of the T cell-specific lck promoter to abrogate the concentration gradient to which T cells normally respond. Overexpression of mCCL21 in T cells resulted in defects in CCL21- and CCL19-induced T-cell chemotaxis, node T-cell subpopulations, and lymph node architecture. The regulation of T-cell trafficking in secondary lymphoid tissues by CCL21 is therefore a tightly regulated system that can be altered by changes in the level of environmental CCL21 protein.
Th17 Pathway-Mediated Immunopathogenesis of Schizophrenia: Mechanisms and Implications (2014)

Schizophrenia is a highly complex and severe neuropsychiatric disorder with an unknown etiopathology. Evidence for a dysregulated immune system in both the risk for and progression of schizophrenia has recently been overwhelming. Importantly, chronic low-grade inflammation both in the periphery and central nervous system has been shown to contribute predominantly to the pathogenesis of schizophrenia in a subset of individuals. Inflammation in the central nervous system is mediated by a range of proinflammatory cytokines, resident immune cells such as microglia, and brain infiltrating peripheral immunocompetent cells, such as T lymphocytes. Recently, Th17 cells, a subset of T helper cells have emerged as crucial players in mucosal defense against infections. It is linked to atopic, inflammatory, and autoimmune disorders. The risk factors/mechanisms leading to low-grade inflammation in schizophrenia are diverse and include infectious agents, stress, trauma, environmental toxins, genetic vulnerability, physical inactivity, obesity, poor diet, and sleep disruption. Herein, we propose that fetal programming of cellular immune components driven by intrauterine adversity can lead to the generation of long-lasting effector/memory Th17 cells. Th17 cells can disrupt the blood-brain barrier, infiltrate the central nervous system, and, along with other cytokines and microglia, lead to neuroprogression through neuroinflammation in schizophrenia.
Targeting Cancer with Small-Molecular-Weight Kinase Inhibitors (2011)

Protein and lipid kinases fulfill essential roles in many signaling pathways that regulate normal cell functions. Deregulation of these kinase activities lead to a variety of pathologies ranging from cancer to inflammatory diseases, diabetes, infectious diseases, cardiovascular disorders, cell growth and survival. 518 protein kinases and about 20 lipid-modifying kinases are encoded by the human genome, and a much larger proportion of additional kinases are present in parasite, bacterial, fungal, and viral genomes that are susceptible to exploitation as drug targets. Since many human diseases result from overactivation of protein and lipid kinases due to mutations and/or overexpression, this enzyme class represents an important target for the pharmaceutical industry. Approximately one third of all protein targets under investigation in the pharmaceutical industry are protein or lipid kinases.The kinase inhibitors that have been launched, thus far, are mainly in oncology indications and are directed against a handful of protein and lipid kinases. With one exception, all of these registered kinase inhibitors are directed toward the ATP-site and display different selectivities, potencies, and pharmacokinetic properties. At present, about 150 kinase-targeted drugs are in clinical development and many more in various stages of preclinical development. Kinase inhibitor drugs that are in clinical trials target all stages of signal transduction from the receptor protein tyrosine kinases that initiate intracellular signaling, through second-messenger-dependent lipid and protein kinases, and protein kinases that regulate the cell cycle.This review provides an insight into protein and lipid kinase drug discovery with respect to achievements, binding modes of inhibitors, and novel avenues for the generation of second-generation kinase inhibitors to treat cancers.
Gas transport and thermal characterization of mono‐ and di‐polyethylene films used for food packaging (2005)

Abstract The permeability of carbon dioxide, oxygen, nitrogen, and air through commercial monolayer and multilayer films, based on polyethylene (PE), biaxially oriented polypropylene (BOPP), and polyamide (PA), used for food packaging is reported. The influence of temperature (from 10 to 60°C) on permeability and DSC characteristics changes was also analyzed. Literature data for gas permeability of the mentioned monofilms are quite variable due to differences in additives, thermal history, and crystallinity. In this work, the highest gas permeability is obtained for PE film at the higher temperature (50–60°C). Laminates exhibit different gas permeation behavior from that of monofilms. Generally, gas solubility coefficient increases at higher temperature (with an exception of PA/PE and BOPPcoex.met/PE), being higher for monofilms in comparison with laminates, while diffusion coefficients are lower for monofilms in comparison with laminates. The temperature dependence of the permeability, diffusivity, and solubility of gases shows two different regions in PE, BOPPcoex/PE (10–40°C and 40–60°C), PA/PE, and BOPPcoex.met (10–30°C and 40–60°C) films. Correlation between activation energies for permeation and diffusion as well as heat of sorption and 17 gas properties is performed. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1590–1599, 2006
New perspectives in vaccine development: mucosal immunity to infections. (1993)

In this review, we focus on six key areas currently receiving attention in the mucosal immune system. These six areas are of considerable importance for development of vaccines. They are (a) the necessity to understand the unique features of the mucosal immune system; (b) the possibility that the common mucosal immune system may contain distinct compartments; (c) differences in antigen uptake and in types of antigen-presenting cells in mucosal inductive and effector sites; (d) more careful consideration of mucosal memory in vaccine development; (e) recent studies, which show that oral vaccines induce T-helper (Th)-cell subsets that regulate mucosal IgA responses; and (f) the mechanisms whereby mucosal S-IgA and T cells provide mucosal immune protection. An example of the above suffices to illustrate why the selected areas are of importance in vaccine development. Oral immunization preferentially induces type 2 Th (Th2) cell responses that directly correlate with antigen-specific IgA responses in mucosal effector sites. It is likely that activated, antigen-specific Th2 cells that are induced in Peyer's patches are continuously supplied to mucosal effector sites for regulation of IgA responses. These Th2 cells are producing cytokines such as interleukin (IL)-5 and IL-6 and these cytokines may direct antigen-specific surface IgA-positive B cells to become IgA-producing plasma cells. Nevertheless, additional studies will be required to establish that IgA responses to T-cell-dependent antigens depend on Th2 cell-derived help. What are the implications of these studies for current oral vaccines, including novel antigen delivery systems? The most obvious would be that vaccines should be optimized for induction of Th2-cell responses in IgA inductive sites such as the gut-associated lymphoreticular tissues. It is now clear that induction of Th2-type responses in both mucosal inductive and mucosal effector sites are essential for oral vaccines to induce S-IgA responses. However, antigens delivered by live vectors such as Salmonella typhimurium in the murine system and S. typhi in humans must consider T-cell responses induced against a live vector in addition to the inserted recombinant antigen. In this regard, it has been shown that these microorganisms induce cell-mediated immunity responses that largely result from Th1-type cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Synthesis and Characterization of the Mn(II) Complex of [15]aneN5 (1988)

The complex Mn[15]aneN5CIPF6 has been prepared by the reaction of MnCI2 [15]aneN5.3HPF6, and NaOH in water ([15]aneN5 is 1,4,7,10,13-pentaazacyclopentadecane). The complex is obtained as a white solid formulated as [Mn(C10H25N5)Cl](PF6).3/2H2O. It is a 2: 1 electrolyte in H2O and a 1:1 electrolyte in CH3CN, The complex contains high spin Mn(II), μeff = 5.83 B.M., and the EPR spectrum of the polycrystalline solid is indicative of rhombic symmetry at the metal site. The proton NMR relaxation enhancement of aqueous solvent by the complex is 2.3 mM−1S −1 at 24 MHz and 25°C and is indicative of one rapidly exchanging water molecule in the coordination sphere of the solvated complex. The stability constant for the formation of the complex in aqueous solution as measured by potentiometric titration (IogK = 10.7) is four orders of magnitude greater than the comparable linear polyamine. In all, the characterization data are consistent with Mn(lI) strongly bound to a distorted or folded ligand and able to accommodate only one additional ligand.
The FPX KCPSM Module: An Embedded, Reconfigurable Active Processing Module for the Pield Programmable Port Extender (FPX) (2001)

While hardware plugins are well suited for processing data with high throughput, software plugins are well suited for implementing complex control functions. A plugin module has been implemented for the FPX that executes software on an embedded soft-core processor. By including this module in an FPX design, it is possible to implement active networking functions on the FPX using both hardware and software. The KCPSM, an 8-bit microcontroller developed by Xilinx Corp., has been embedded into an FPX module. The module includes circuits to be reprogrammed over the network and to execute new programs between the processing of data packerts. A sample application, called the FPX KXPSM Module has been developed that illustrates how easily an application can make use of the hybrid system. This module loads the program memory of the KCPSM from an incoming UDP packet, and executes the new program upon receiving a new incoming UDP packet. The resulting circuit runs at 70MHz and occupies 35% on a Xilinx XCV1000E-7-FG680.
N‐Methyl‐l‐amino acid dehydrogenase from Pseudomonas putida (2005)

We found N-methyl-L-amino acid dehydrogenase activity in various bacterial strains, such as Pseudomonas putida and Bacillus alvei, and cloned the gene from P. putida ATCC12633 into Escherichia coli. The enzyme purified to homogeneity from recombinant E. coli catalyzed the NADPH-dependent formation of N-alkyl-L-amino acids from the corresponding alpha-oxo acids (e.g. pyruvate, phenylpyruvate, and hydroxypyruvate) and alkylamines (e.g. methylamine, ethylamine, and propylamine). Ammonia was inert as a substrate, and the enzyme was clearly distinct from conventional NAD(P)-dependent amino acid dehydrogenases, such as alanine dehydrogenase (EC 1.4.1.1). NADPH was more than 300 times more efficient than NADH as a hydrogen donor in the enzymatic reductive amination. Primary structure analysis revealed that the enzyme belongs to a new NAD(P)-dependent oxidoreductase superfamily, the members of which show no sequence homology to conventional NAD(P)-dependent amino acid dehydrogenases and opine dehydrogenases.
Characterization of irreversible electroporation on the stomach: A feasibility study in rats (2019)

Irreversible electroporation (IRE) is a newly developed non-thermal ablative therapy. During the IRE procedure, the permeability of the cell membrane is irreversibly changed by application of high-energy pulses across the tissue. This induces the breakdown of cell homeostasis, and thereby cell death. Here, we present an in vivo study to demonstrate IRE ablation of gastric tissue and characterize the changes that occur with time therein. No significant complications were observed in the test rats during the experiment. The electroporated tissues exhibited apoptosis at 10, 24 and 48 h after IRE ablation. The apoptosis peaked at 10 h after IRE and then declined, suggesting that the ablated tissue rapidly recovered owing to intense metabolic activity. In addition, the electroporated tissues exhibited morphological changes such as pyknosis and karyorrhexis, while histological analysis showed that the blood vessels were preserved. Interestingly, electroporation greatly affected the mucosa and muscularis propria, but not the submucosa and serosa. This study suggests that IRE could potentially be used as a minimally invasive treatment for early gastric cancer that does not exhibit lymph node metastasis or dysplasia.
Optical parametric interactions in isotropic materials using a phase-corrected stack of nonlinear dielectric plates (1975)

Optical parametric interactions are analyzed for collinear three-frequency processes in a series of plates of isotropic nonlinear dielectric. Phase-velocity mismatch caused by refractive-index dispersion is compensated by making each plate one coherence length thick and orienting consecutive plates so the nonlinear polarization is shifted in phase by π. Parametric transfer of energy then proceeds constructively along the axis of propagation. For second harmonic generation, frequency upconversion and downconversion, and parametric amplification the output intensity is proportional to the square of the number of phase-corrected plates. The conversion efficiency is the same as for a hypothetical phase-velocity-matched interaction in the same nonlinear material, except that the nonlinear susceptibility is effectively reduced by a factor of 2/π.This method can be used to obtain efficient nonlinear interactions over frequency ranges previously precluded by lack of suitable transparent birefringent crystals and for large-aperture configurations for generating high powers.
Rapid Redistribution of CD20 to a Low Density Detergent-insoluble Membrane Compartment (1998)

CD20 is a B cell integral membrane protein capable of initiating growth-modulating signals in human B lymphocytes upon its engagement with monoclonal anti-CD20 antibodies. In this report, we demonstrate that treatment of B cells with CD20 antibodies induces rapid redistribution of CD20 into a detergent-insoluble membrane compartment. Redistribution is detected as early as 15 s, following antibody addition, and involves up to 95% of CD20 molecules, depending on the antibody used. All of the detergent-insoluble CD20 was found in the low density fractions of sucrose density gradients, indicating that CD20 redistributes to glycolipid-rich membrane domains, analogous to caveolae in some cell types. As CD20 has previously been shown to associate with Src family tyrosine kinases, their co-existence in these compartments suggests a link to the role of CD20 in signal transduction. This study provides insight into the mechanism by which CD20 communicates signals to the cell interior and indicates that the search for membrane-proximal intracellular signaling partners should be directed to the Triton-insoluble fraction.
Differential roles of checkpoint kinase 1, checkpoint kinase 2, and mitogen-activated protein kinase–activated protein kinase 2 in mediating DNA damage–induced cell cycle arrest: implications for cancer therapy (2006)

Mammalian cells initiate cell cycle arrest at different phases of the cell cycle in response to various forms of genotoxic stress to allow time for DNA repair, and thus preserving their genomic integrity. The protein kinases checkpoint kinase 1 (Chk1), checkpoint kinase 2 (Chk2), and mitogen-activated protein kinase-activated protein kinase 2 (MK2) have all been shown to be involved in cell cycle checkpoint control. Recently, cell cycle checkpoint abrogation has been proposed as one way to sensitize cancer cells to DNA-damaging agents due to the expected induction of mitotic catastrophe. Due to their overlapping substrate spectra and redundant functions, it is still not clear which kinase is mainly responsible for the cell cycle arrests conferred by clinically relevant chemotherapeutics. Thus, the issue remains about which kinase is the most therapeutically relevant target and, more importantly, whether multiple kinases might need to be targeted to achieve the best efficacy in light of recent studies showing superior efficacy for pan-receptor tyrosine kinase inhibitors. To clarify this issue, we investigated the roles of the three kinases in response to different genotoxic stresses through small interfering RNA-mediated specific target knockdowns. Our result showed that only the down-regulation of Chk1, but not of Chk2 or MK2, abrogated camptothecin- or 5-fluorouracil-induced S-phase arrest or doxorubicin-induced G(2)-phase arrest. This was followed by mitotic catastrophe and apoptosis. Moreover, double inhibition of Chk1 and Chk2 failed to achieve better efficacy than Chk1 inhibition alone; surprisingly, inhibition of MK2, in addition to Chk1 suppression, partially reversed the checkpoint abrogation and negated mitotic catastrophe. We further showed that this is due to the fact that in MK2-deficient cells, Cdc25A protein, which is critically required for the mitotic progression following checkpoint abrogation, becomes greatly depleted. In summary, our findings show that Chk1 is the only relevant checkpoint kinase as a cancer drug target and inhibition of other checkpoint kinases in addition to Chk1 would be nonproductive.
Cycloartane Triterpene Glycosides from the Roots of Astragalus brachypterus and Astragalus microcephalus (1998)

Three new cycloartane-type triterpene glycosides, brachyosides A (1), B (3), and C (2), from the roots of Astragalus brachypterus and one new glycoside, cyclocephaloside II (4), from the roots of Astragalusmicrocephalus have been isolated together with five known saponins, astragalosides I, II, and IV, cyclocanthoside E, and cycloastragenol. The structures of the new compounds were established as 3-O-[beta-D-xylopyranosyl(1-->3)-beta-D-xylopyranosyl-6-O-beta-D-gluc opyranosyl-3beta,6alpha,16beta,24(S),25-pentahydrox ycycloartane (1), 3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-24-O-beta-D-glucop yranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxyc ycloartane (2), 20(R),24(S)-epoxy-6-O-beta-D-glucopyranosyl-3beta,6alpha,16beta , 25-tetrahydroxycycloartane (3), and 20(R), 24(S)-epoxy-3-O-(4'-O-acetyl)-beta-D-xylopyranosyl-6-O-beta-D-glucopy ranosyl-3beta,6alpha,16beta,25-tetrahydroxycycloart ane (4). For the structure elucidations, 1D- and 2D-NMR experiments and FABMS were used.
Analysis of immunoglobulin mRNA in murine myeloma cell variants defective in the synthesis of the light or heavy polypeptide chains. (1982)

Abstract The immunoglobulin (Ig) mRNA species in spontaneously arisen myeloma cell variants, which lose the ability to synthesize the Ig heavy and/or light chains, were analyzed using the RNA blotting technique. Nicktranslated recombinant plasmid clones containing Κ- and γ-chain sequences were used as hybridization probes. It was found that the MPC 11 clone 4T00.1L1 and the MOPC 21 clone NSI, which are known to produce small quantities of the γ2b and γ1 heavy chains, respectively, contained correspondingly small amounts of y-mRNA molecules; although the γ-mRNA of clone 4T00.1L1 was of normal size (1.9 kilo bases [kb]), the γ-mRNA of clone NSI was of a smaller size (1.3 kb). Reduced quantities of a smaller sized γ heavy chain mRNA were also found in the MPC 11 clone 66.2 (1.7 kb) and in MOPC 21 clones P3NP (1.7 kb) and 653 (1.7 kb), which do not produce detectable amounts of γ heavy chains. The only nonproducer clone that seemed to be completely devoid of the γ-mRNA was clone NP2 (MPC 11). With regard to the Κ-mRNA, the nonproducer MOPC 21 variants P3NP and 653 were found to contain appreciable amounts of smaller or normal-sized κ-mRNA, respectively. In contrast, the MPC 11 nonproducer clone NP2 did not contain detectable levels of the full-length 1.2 kb κ-mRNA, even though it did produce the 0.8 kb κ-mRNA fragment, which is known to be present in all the MPC 11 clones. It would thus appear that most of the myeloma cell variants that lost the ability to produce Ig chains contain reduced to normal quantities of smaller or normal-sized Ig mRNA molecules. These findings indicate that in many of these mutants the respective Ig genes are not fully deleted.
Karyotypic complexity of the NCI-60 drug-screening panel. (2003)

We used spectral karyotyping to provide a detailed analysis of karyotypic aberrations in the diverse group of cancer cell lines established by the National Cancer Institute for the purpose of anticancer drug discovery. Along with the karyotypic description of these cell lines we defined and studied karyotypic complexity and heterogeneity (metaphase-to-metaphase variations) based on three separate components of genomic anatomy: (a) ploidy; (b) numerical changes; and (c) structural rearrangements. A wide variation in these parameters was evident in these cell lines, and different association patterns between them were revealed. Analysis of the breakpoints and other specific features of chromosomal changes across the entire set of cell lines or within particular lineages pointed to a striking lability of centromeric regions that distinguishes the epithelial tumor cell lines. We have also found that balanced translocations are as frequent in absolute number within the cell lines derived from solid as from hematopoietic tumors. Important similarities were noticed between karyotypic changes in cancer cell lines and that seen in primary tumors. This dataset offers insights into the causes and consequences of the destabilizing events and chromosomal instability that may occur during tumor development and progression. It also provides a foundation for investigating associations between structural genome anatomy and cancer molecular markers and targets, gene expression, gene dosage, and resistance or sensitivity to tens of thousands of molecular compounds.
ANDROTEST©: A Structured Interview for the Screening of Hypogonadism in Patients with Sexual Dysfunction (2006)

ANDROTEST is a quick and easy-to-administer interview that provides scores for the screening of male hypogonadism in patients with sexual dysfunction.
Transforming properties of YAP , a candidate oncogene on the chromosome 11q22 amplicon (2006)

In a screen for gene copy-number changes in mouse mammary tumors, we identified a tumor with a small 350-kb amplicon from a region that is syntenic to a much larger locus amplified in human cancers at chromosome 11q22. The mouse amplicon contains only one known gene, Yap, encoding the mammalian ortholog of Drosophila Yorkie (Yki), a downstream effector of the Hippo(Hpo)-Salvador(Sav)-Warts(Wts) signaling cascade, recently identified in flies as a critical regulator of cellular proliferation and apoptosis. In nontransformed mammary epithelial cells, overexpression of human YAP induces epithelial-to-mesenchymal transition, suppression of apoptosis, growth factor-independent proliferation, and anchorage-independent growth in soft agar. Together, these observations point to a potential oncogenic role for YAP in 11q22-amplified human cancers, and they suggest that this highly conserved signaling pathway identified in Drosophila regulates both cellular proliferation and apoptosis in mammalian epithelial cells.