gebhart/patrepeval huggingface dataset:
Brain derived versican V2 is a potent inhibitor of axonal growth (2000)

In this paper, we identify the chondroitin sulfate proteoglycan versican V2 as a major inhibitor of axonal growth in the extracellular matrix of the mature central nervous system. In immunohistochemical and in situ hybridization experiments we show that this tissue-specific splice variant of versican is predominantly present in myelinated fiber tracts of the brain and in the optic nerve, most likely being expressed by oligodendrocytes. We demonstrate that isolated versican V2 strongly inhibits neurite outgrowth of central and peripheral neurons in stripe-choice assays using laminin-1 as permissive substrate. The inhibitory character of versican V2 is maintained after removal of chondroitin sulfate and N- and O-linked oligosaccharide side chains, but it is abolished after core protein digestion with proteinase-K. Our data support the notion, that intact versican V2 prevents excessive axonal growth during late phases of development and hereby participates in the structural stabilization of the mature central nervous system.
Controlling polarization of quantum-dot surface-emitting lasers by using structurally anisotropic self-assembled quantum dots (1997)

Polarization control is achieved in vertical-cavity surface-emitting lasers (VCSELs) by using structurally anisotropic self-assembled quantum dots (QDs) as active layers. The dot shape is long in the [01̄1] direction on the (100) surface. The photoluminescence from the dots has a polarization dependence whose intensity along the [01̄1] direction is 1.37 times stronger than that along the orthogonal [011] direction. The QD VCSEL operates at the wavelength of the QD ground state transition. Lasing emission shows polarization along the [01̄1] direction and an orthogonal polarization suppression ratio of 18 dB.
Nucleic Acid Immunizations (1998)

This unit provides protocols for two broadly used methods of DNA immunization: saline injections and gene gun deliveries of DNA. Saline injections deliver DNA into extracellular spaces; gene gun deliveries bombard DNA directly into cells. Support protocols present methods for preparation of DNA-coated gold beads, creation of cartridges containing these beads, and optimization of gene gun parameters. Issues relating to plasmid vectors, DNA preparation and doses, and immunization regimens are also discussed. Expression library immunizations, genetic and conventional adjuvants, alternative boosts, neonatal immunizations, and approaches to mucosal delivery of DNA are covered in the commentary.
Rapid and Specific Molecular Identification of Methicillin-Resistant Staphylococcus aureus in Endotracheal Aspirates from Mechanically Ventilated Patients (1998)

Multiplex amplification of femA and mecA genetic determinants allowed an early and rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) in endotracheal aspirates of mechanically ventilated patients. femA and/or mecA amplification and bacteriological results were concordant in 57 of 60 samples. In all three discrepant cases, complementary bacteriological tests confirmed the presence of MRSA first identified by molecular analysis. These results underline the value and rapidity of this molecular diagnosis for MRSA infection and control surveillance in intensive care units. Rapid MRSA detection is expected to have a significant clinical impact not only on patient outcome but also on the costs for isolation and treatment.
A file system interface for concurrent access (1994)

The paper introduces a transparent service .for synchronized replication across loosely-connected, heterogeneous file systems, and it focuses on the part of the service that supports transactional synchronization. The transaction paradigm is useful for grouping together the file accesses in a program that are logically connected, such that each group of accesses is synchronized as an atomic unit. The service, Parrot, is implemented as a library that an application links and runs in its own address space. The library redefines and extends the file system interface open/close/read/write, while preserving its syntax and semantics. Parrot implements a read-one write-all synchronization protocol that (1) guarantees consistency across all copies of each replicated file at the granularity of individual read and write operations and (2) supports transactional synchronization for sequences of read and write operations on one or more files.
Dig-Music: An on Demand Digital Musical Selection System Utilizing CATV Facilities (1982)

The extension of CATV facilities to every urban community and most rural communities of more than a few hundred households coupled with the increased channel capacity of these CATV facilities will result in a severe "software" shortage. There is a proliferation of new services being offered and in the planning stage, both "free" and subscriber based, but it is unlikely that these services will effectively utilize the total capacity of the newer systems which provide a bandwidth of 400 Mhz and higher. This paper describes Dig-Music, a proposed service which provides musical and voice offerings to subscribers on demand, a specialized service which would effectively utilize one or more channels. The selections are stored in digital form at the head-end of CATV systems and are transmitted to the subscriber on request. The major challenge associated with such a system is that high quality music reproduction from digital data requires a minimum of one- half million bits/second (1) assuming no compression.
Expert system for data acquisition to achieve a constant signal-to-noise ratio: application to imaging of DNA sequencing gels (1993)

Normally, data acquisition and processing in chemical measurements are based on equal time (effort) for each data point. This leads to uneven signal-to-noise ratios (S/N) for each point. We present an expert system which decides in real time whether adequate S/N has been achieved for each point. If so, that data point will be omitted in all further acquisition or processing operations, greatly increasing the overall efficiency. The special case of analyzing DNA sequencing gels is tested with this scheme. A factor of 7.6 reduction in effort is demonstrated for a data set of 384 x 250 pixels, which normally would require 6 million sequential operations (64 frames).
Selective subcellular redistributions of protein kinase C isoforms by chemical hypoxia (1999)

The mechanisms of neuronal degeneration following hypoxia/ischemia remain undefined, but the processes include increases in neurotransmitter release, elevation of cytosolic-free calcium concentration, and changes in signal transduction pathways. Activation of the multigene family of protein kinase C (PKC) has been associated with the release of neurotransmitter and the survival of neurons. Therefore, to understand which PKC isozymes are involved in hypoxia/ischemia-induced neuronal degeneration, we examined PKC isozymes after chemical hypoxia (i.e., KCN exposure) in PC12 cells. Cell toxicity, as measured by lactate dehydrogenase (LDH) release, was increased significantly by KCN in glucose-free DMEM and was exaggerated by acute 12-O-tetradecanoyl phorbol-13-acetate (TPA) pretreatment. Under parallel conditions, KCN elevated cytosolic-free calcium ([Ca2+]i) in glucose-free but not in glucose containing DMEM, and TPA pretreatment did not exaggerate KCN's effect on [Ca2+]i. Thus, increases in [Ca2+]i are not sufficient for the synergistic toxic effect of KCN and TPA. In the glucose-free DMEM, selective PKC isozyme inhibitor Go 6976 at 10 nM completely inhibited KCN-induced LDH release and at higher concentrations (1 μM) inhibited the basal levels of LDH release. The protein levels of PKCs in the nuclear, membrane, and cytosolic fractions were measured by Western blot analysis using antibodies against specific isoforms. Two Ca2+-dependent (−α, −γ) and four Ca2+-independent (−δ, −ϵ, −ζ, and −λ) isozymes were identified and two isozymes (−β and −θ) were not detected in the subcellular fractions of PC12 cells. Treatment of the cells with TPA significantly activated translocation of conventional PKC-γ from the cytosol to the membrane and nuclear fractions and other PKC isozymes (−α, −δ, and −ϵ) from the cytosol to the membrane, but not atypical PKC-ζ and -λ. Although only the levels in the nuclear PKC-γ but not other PKC isozymes were increased significantly following KCN, the levels of cPKC-α and -γ in the membrane mainly—and those and PKC-ϵ in the nucleus—were increased when KCN was combined with TPA. In addition, this condition (TPA + KCN) did not affect the TPA insensitive atypical isozymes, PKC-ζ or -λ. Taking the results together, differential activation/translocation of PKC isozymes by KCN and TPA is important in the regulation of chemical hypoxia-induced cell injury in PC12 cells. J. Neurosci. Res. 56:668–678, 1999. © 1999 Wiley-Liss, Inc.
A straightforward approach towards cyclic peptides via ring-closing metathesis—scope and limitations (2004)

N- and C-terminal diallylated peptides are obtained by several approaches, such as peptide Claisen rearrangement, N- and O- allylation, and the Ugi reaction of allyl-protected components. These diallylated peptides are suitable substrates for ring-closing metathesis and the success of this cyclisation was investigated with respect to the ring size, the position of the allyl moieties and the reaction parameters. In general, excellent yields are obtained for cyclisation of allyl glycine subunits and N-allylated amides, while allyl esters and allyl carbamates often presented serious problems. However, yields of up to 73% were obtained under optimised conditions, and the new generated double bond is formed with excellent trans-selectivity.
Organogenesis and tissue regeneration of fallopian tube: a desired metaplastic transformation of mesodermal stem cells in live animal models (dogs). (2000)

The capacity of stem cells of peritonium of mesodermal origin to undergo metaplastic transformation and form different tissues developed from mesoderm germ layer is exploited with ulterior motive to use it in the management of human diseases. The excised fallopian tube was replaced with a tube on a stent constructed from autogenous peritoneum from a suitable donor site. The effect of the surroundings environment of the new tissue system to which the peritoneum stem cells are now exposed was studied for 3, 6 and 12 months period in live animal models. The gross and histological studies revealed development of all the component of the wall of the fallopian tube. The lumen of the constructed peritoneal tube was well preserved in its whole length including the anastomotic sites. The scientific rationale of the working hypothesis on which the work is based, is discussed.
ADULT NEUROGENESIS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM (2005)

Forty years since the initial discovery of neurogenesis in the postnatal rat hippocampus, investigators have now firmly established that active neurogenesis from neural progenitors continues throughout life in discrete regions of the central nervous systems (CNS) of all mammals, including humans. Significant progress has been made over the past few years in understanding the developmental process and regulation of adult neurogenesis, including proliferation, fate specification, neuronal maturation, targeting, and synaptic integration of the newborn neurons. The function of this evolutionarily conserved phenomenon, however, remains elusive in mammals. Adult neurogenesis represents a striking example of structural plasticity in the mature CNS environment. Advances in our understanding of adult neurogenesis will not only shed light on the basic principles of adult plasticity, but also may lead to strategies for cell replacement therapy after injury or degenerative neurological diseases.
Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies (2013)

Abstract Background Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/ neu , they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2. Methods ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/ neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51 Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines. Results EGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50—80% cytotoxicity against four primary glioblastoma lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133– and CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets. Conclusion High-grade gliomas are suitable for specific targeting by armed ATC. These data, together with additional animal studies, may provide the preclinical support for the use of armed ATC as a valuable addition to current treatment regimens.
Structural Analysis of Human Argonaute-2 Bound to a Modified siRNA Guide (2016)

Incorporation of chemical modifications into small interfering RNAs (siRNAs) increases their metabolic stability and improves their tissue distribution. However, how these modifications impact interactions with Argonaute-2 (Ago2), the molecular target of siRNAs, is not known. Herein we present the crystal structure of human Ago2 bound to a metabolically stable siRNA containing extensive backbone modifications. Comparison to the structure of an equivalent unmodified-siRNA complex indicates that the structure of Ago2 is relatively unaffected by chemical modifications in the bound siRNA. In contrast, the modified siRNA appears to be much more plastic and shifts, relative to the unmodified siRNA, to optimize contacts with Ago2. Structure-activity analysis reveals that even major conformational perturbations in the 3' half of the siRNA seed region have a relatively modest effect on knockdown potency. These findings provide an explanation for a variety of modification patterns tolerated in siRNAs and a structural basis for advancing therapeutic siRNA design.
Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration (2003)

Tight junctions (TJs) create ion-selective paracellular permeability barriers between extracellular compartments. In the organ of Corti of the inner ear, TJs of the reticular lamina separate K(+)-rich endolymph and Na(+)-rich perilymph. In humans, mutations of the gene encoding claudin 14 TJ protein cause profound deafness but the underlying pathogenesis is unknown. To explore the role of claudin 14 in the inner ear and in other tissues we created a mouse model by a targeted deletion of Cldn14. In the targeted allele a lacZ cassette is expressed under the Cldn14 promoter. In Cldn14-lacZ heterozygous mice beta-galactosidase activity was detected in cochlear inner and outer hair cells and supporting cells, in the collecting ducts of the kidney, and around the lobules of the liver. Cldn14-null mice have a normal endocochlear potential but are deaf due to rapid degeneration of cochlear outer hair cells, followed by slower degeneration of the inner hair cells, during the first 3 weeks of life. Monolayers of MDCK cells expressing claudin 14 show a 6-fold increase in the transepithelial electrical resistance by decreasing paracellular permeability for cations. In wild type mice, claudin 14 was immunolocalized at hair cell and supporting cell TJs. Our data suggest that the TJ complex at the apex of the reticular lamina requires claudin 14 as a cation-restrictive barrier to maintain the proper ionic composition of the fluid surrounding the basolateral surface of outer hair cells.
Production, Analysis, and Application of Spatially Resolved Shells in Solid-Phase Polymer Spheres (2002)

Two-photon fluorescence microscopy has been used to interrogate the interior functionality of polymer resin beads. By employing this technique, the spatial distribution of the initial functionality contained within the polymer matrix has been determined. Spatially resolved, concentric shells were then produced synthetically in these polymer spheres via a series of protection/deprotection reactions in which two-photon fluorescence microscopy was employed to monitor each successive step. To demonstrate the potential utility of these techniques in combinatorial screening, a set of beads was prepared containing a unique tripeptide sequence in each of the three concentric shells within each individual bead. The set was then screened for the binding affinity of each tripeptide toward a fluorescent ligand.
The Novel Anticonvulsant Drug, Gabapentin (Neurontin), Binds to the α2δ Subunit of a Calcium Channel (1996)

Gabapentin (1-(aminomethyl)cyclohexane acetic acid; Neurontin) is a novel anticonvulsant drug, with a mechanism of action apparently dissimilar to that of other antiepileptic agents. We report here the isolation and characterization of a [3H]gabapentin-binding protein from pig cerebral cortex membranes. The detergent-solubilized binding protein was purified 1022-fold, in a six-step column-chromatographic procedure, with a yield of 3.9%. The purified protein had an apparent subunit Mr of 130,000, and was heavily glycosylated. The partial N-terminal amino acid sequence of the Mr 130,000 polypeptide, EPFPSAVTIK, was identical to that reported for the alpha2delta subunit of the L-type Ca2+ channel from rabbit skeletal muscle (Hamilton, S. L., Hawkes, M. J., Brush, K., Cook, R., Chang, R. J., and Smilowitz, H. M. (1989) Biochemistry 28, 7820-7828). High levels of [3H]gabapentin binding sites were found in membranes prepared from rat brain, heart and skeletal muscle. Binding of [3H]gabapentin to COS-7 cells transfected with alpha2delta cDNA was elevated >10-fold over controls, consistent with the expression of alpha2 delta protein, as measured by Western blotting. Finally, purified L-type Ca2+ channel complexes were fractionated, under dissociating conditions, on an ion-exchange column; [3H]gabapentin binding activity closely followed the elution of the alpha2 delta subunit. [3H]Gabapentin is the first pharmacological agent described that interacts with an alpha2delta subunit of a voltage-dependent Ca2+ channel.
Acute treatment with the PPARγ agonist pioglitazone and ibuprofen reduces glial inflammation and Aβ1–42 levels in APPV717I transgenic mice (2005)

Neuritic plaques in the brain of Alzheimer's disease patients are characterized by beta-amyloid deposits associated with a glia-mediated inflammatory response. Non-steroidal anti-inflammatory drug (NSAID) therapy reduces Alzheimer's disease risk and ameliorates microglial reactivity in Alzheimer's disease brains; however, the molecular mechanisms subserving this effect are not yet clear. Since several NSAIDs bind to and activate the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) which acts to inhibit the expression of proinflammatory genes, this receptor appears a good candidate to mediate the observed anti-inflammatory effects. Recent data in vitro suggested that NSAIDs negatively regulate microglial activation and immunostimulated amyloid precursor protein processing via PPARgamma activation. We report that an acute 7 day oral treatment of 10-month-old APPV717I mice with the PPARgamma agonist pioglitazone or the NSAID ibuprofen resulted in a reduction in the number of activated microglia and reactive astrocytes in the hippocampus and cortex. Drug treatment reduced the expression of the proinflammatory enzymes cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS). In parallel to the suppression of inflammatory markers, pioglitazone and ibuprofen treatment decreased beta-secretase-1 (BACE1) mRNA and protein levels. Importantly, we observed a significant reduction of the total area and staining intensity of Abeta1-42-positive amyloid deposits in the hippocampus and cortex. Additionally, animals treated with pioglitazone revealed a 27% reduction in the levels of soluble Abeta1-42 peptide. These findings demonstrate that anti-inflammatory drugs can act rapidly to inhibit inflammatory responses in the brain and negatively modulate amyloidogenesis.
An important developmental role for oligosaccharides during early embryogenesis of cyprinid fish (1997)

Derivatives of chitin oligosaccharides have been shown to play a role in plant organogenesis at nanomolar concentrations. Here we present data which indicate that chitin oligosaccharides are important for embryogenesis in vertebrates. We characterize chitin oligosaccharides synthesized in vitro by zebrafish and carp embryos in the late gastrulation stage by incorporation of radiolabeled N-acetyl-D-[U14C]glucosamine and by HPLC in combination with enzymatic conversion using the Bradyrhizobium NodZ alpha-1, 6-fucosyltransferase and chitinases. A rapid and sensitive bioassay for chitin oligosaccharides was also used employing suspension-cultured plant cells of Catharanthus roseus. We show that chitin oligosaccharide synthase activity is apparent only during late gastrulation and can be inhibited by antiserum raised against the Xenopus DG42 protein. The DG42 protein, a glycosyltransferase, is transiently expressed between midblastula and neurulation in Xenopus and zebrafish embryogenesis. Microinjection of the DG42 antiserum or the Bradyrhizobium NodZ enzyme in fertilized eggs of zebrafish led to severe defects in trunk and tail development.
Heterogeneity of recombinant human antithrombin III expressed in baby hamster kidney cells. Effect of glycosylation differences on heparin binding and structure (1993)

To determine the effects of differences in glycosylation on the structure and functional properties of recombinant human antithrombin (rHAT), we have characterized the properties of the recombinant protein overexpressed by baby hamster kidney cells. Three forms of rHAT, I-III, were isolated which differed in affinity for heparin. Form I had the lowest affinity and contained a high proportion of highly branched complex carbohydrate. Form II had higher affinity and contained both complex and high mannose-type chains. Form III had the highest affinity and was similar to form II in the type of carbohydrate present, but had a lower level of glycosylation, consistent with the absence of carbohydrate at one of the four glycosylation sites. 1H NMR spectra of plasma HAT and rHAT forms I-III suggested very similar protein structures for all forms. Heparin pentasaccharide produced almost identical NMR perturbation difference spectra. The only functional difference found was in the rates of inactivation of factor Xa. Forms II and III gave second order rate constants similar to that of plasma HAT, whereas form I gave a biphasic inhibition, with the first phase having a rate about four times that of the other forms. We conclude that carbohydrate heterogeneity does not alter the structure of the HAT polypeptide or the heparin-induced conformational change, but does affect the heparin affinity and can alter the rate of proteinase inhibition.